To explore the toxicological profile of methanol extract of Chlorophytum alismifolium (MECA) tubers in Wistar rats. Methods: MECA was subjected to acute and sub-acute studies which were conducted according to Organiza...To explore the toxicological profile of methanol extract of Chlorophytum alismifolium (MECA) tubers in Wistar rats. Methods: MECA was subjected to acute and sub-acute studies which were conducted according to Organization for Economic Co-operation and Development (OECD 425 and 407 guidelines respectively). In the acute toxicity experiment, a limit test (5000 mg/kg) was administered to five rats and monitored for 2 weeks. The sub-acute studies were conducted on 4 groups of rats. The first group served as control, while the 2nd, 3rd and 4th groups received MECA (150, 300 and 600 mg/kg respectively). The treatments were given orally and daily for 4 weeks. At the end of the experiment (29th day), the animals were euthanized to obtain blood samples and organs for haematological, biochemical and histological evaluations. Results: Acute toxicity study showed that the oral median lethal dose was >5000 mg/kg. In the sub-acute studies, the results showed no significant (P>0.05) changes in the haematological, hepatic and renal indices compared to control animals. In the fourth week, a significant (P<0.01) increase in body weight of the rats was observed at 150 mg/kg and 600 mg/kg compared to week one. However, there were no major changes in the organ/body weights of the rats. Histological examination of the kidney showed slight glomerular adhesion and tubular distortion. Moderate hepatic necrosis was observed at 150 mg/kg and 300 mg/kg. Conclusions: The results of this research revealed that the MECA tubers is virtually non-toxic after acute administration and it has low sub-acute toxicity potential in rats.展开更多
Rumex abyssinica Jacq. (Polygonaceae) is locally used in management of allergies and female reproductive healthcare;whereas Mentha spicata L. (Lamiaceae) is used to treat gastrointestinal and respiratory distress, dan...Rumex abyssinica Jacq. (Polygonaceae) is locally used in management of allergies and female reproductive healthcare;whereas Mentha spicata L. (Lamiaceae) is used to treat gastrointestinal and respiratory distress, dandruff, halitosis and malaria in Uganda. Owing to the paucity of data on their safety profiles, this study evaluated the acute and sub-acute toxicities of 70% ethanolic leaf extracts of both plants in mice and Wistar albino rats. The oral acute toxicity of both plants was evaluated in Swiss mice of 7-8 weeks old (16-22 g) body weight and LD50 determined. Sub-acute toxicity was evaluated in Wistar albino rats (6 per group) at dose rates of 500, 1000 and 1500 mg/kg for 28 days. The LD50 of R. abyssinica and M. spicata in mice was 7727 mg/kg and 13,606 mg/kg body weight, respectively. General signs of toxicity due to large doses of both plants extract included hyperurination, abdominal muscle twitches and convulsions. In the sub-acute toxicity test, rats treated with both extracts did not exhibit any clinical signs of toxicity;no mortality and changes in body weight were observed. R. abyssinica did not cause significant changes in haematological indices, except a significant increase in HCT (p 0.05). However, a dose dependant significant decrease in HCT (p 0.05) and a significant increase (p 0.05) in the levels of WBC, LMY and MCHC were observed in rats treated with M. spicata extract. Biochemical test showed that both extracts caused a significant dose dependent increase (p 0.05) in levels of ALT and ALP. Marked increase in the levels of AST was also observed in rats treated with M. spicata extract. Of the two extracts, only rats treated with </展开更多
The inhibition of acetylcholinesterase (ACHE) activity has been widely used as a biomarker in an animal exposed to the pesticides. However, the interaction of extensively used organocarbamate insecticide, carbofuran, ...The inhibition of acetylcholinesterase (ACHE) activity has been widely used as a biomarker in an animal exposed to the pesticides. However, the interaction of extensively used organocarbamate insecticide, carbofuran, with the nervous system of the aquatic organisms is not properly studied. AChE is a key enzyme which catalyses the hydrolysis of acetylcholine, a neurotransmitter at the neuromuscular junctions, and thus regulates the neurotransmission system. In the present study, we have evaluated the impact of sub-acute concentrations (0.01 and 0.02 mg/L i.e. 1/20th and 1/10th of LC50) of carbofuran on the activity of acetylcholinesterase,from different tissues of Clarias batrachus, a fresh water teleost, after 96 hr and 15 days exposure periods in vivo. The carbofuran significantly reduced the activity of AChE in different tissues of C. batrachus at both concentrations and periods of exposure. The greater inhibition of AChE activities were recorded in fish tissues at higher carbofuran concentration (0.02 mg/L) after longer (15days) treatment period. The inhibition of AChE activity in all fish tissues tested was dependent on pesticide concentration and the duration of treatment. AChE from the tissues of C. batrachus was found to be a true cholinesterase as it was completely inhibited by the small concentration (nM) of eserine as tested in vitro. It was found that carbofuran at very low concentration exerted significant inhibitory effect on AChE activity in fish tissues.展开更多
AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided...AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.展开更多
Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed...Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.展开更多
No data were available on the acute oral toxicity, short-term oral toxicity of vegetable carbon in animals. This study was designed to evaluate the safety of two commercially available dietary bamboo charcoal powders...No data were available on the acute oral toxicity, short-term oral toxicity of vegetable carbon in animals. This study was designed to evaluate the safety of two commercially available dietary bamboo charcoal powders（BCP1 and BCP2）. The size distribution of the two powders was determined by a Mastersizer 2000 laser particle size analyzer prior to the in vivo safety studies. For the acute toxicity study, a single dose of 11.24 g/kg body weight of BCP1 and BCP2 was given once orally to healthy Sprague-Dawley（SD） rats. Mortality and clinical symptoms were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. In the repeated dose 28-day oral toxicity study, BCP1 and BCP2 were administered orally at doses of 2.81, 5.62, and 11.24 g/kg body weight for 28 days to SD rats. Animals were sacrificed and organs and blood samples were analyzed. Results showed that both BCP1 and BCP2 were micro-sized and various in size. In the acute toxicity and the repeated dose 28-day oral toxicity studies, BCP caused neither mortality nor visible signs of toxicity in rats. No significant differences were found in the relative organ weights or in biochemical parameters in BCP treated groups compared to a control group. No treatment-related histological changes were observed in the organs of these animals. Based on these data, it is concluded that the median lethal dose（LD50） of BCP for both male and female rats is more than 11. 24 g/kg body weight and the no-observed-adverse-effect level（NOAEL） is 〉11.24 g/kg body weight for 28 days.展开更多
Background: M. oleifera is a highly valued medicinal plant used widely from time immemorial to treat various ailments. However, with continued un-standardized use of the plant leaves, studies have reported organ toxic...Background: M. oleifera is a highly valued medicinal plant used widely from time immemorial to treat various ailments. However, with continued un-standardized use of the plant leaves, studies have reported organ toxicity to the liver, kidney and the heart. As communities continue to use M. oleifera leaves for its medicinal and nutritional values, there is need to find an antidote for its hepatotoxicity. Aim: The study established the reversal effect of N-Acetyl Cysteine (NAC) on M. oleifera aqueous leaf extract-induced hepatotoxicity in Wistar albino rats. Methods: Twenty-four (24) rats received a toxic dose (8.05 g/kg bwt) of M. oleifera leaf extract for 28 days to cause sub-acute hepatotoxicity. They were divided into 4 groups of 6 rats each. Group I received 1 ml normal (control group), Group II received 1000 ng/kg NAC, Group III received 1200 mg/kg NAC and Group IV received 1500 mg/kg NAC. Another group of 6 rats (Group V) received 0.75 mg/kg Paracetamol to cause hepatotoxicity. Group V (a positive control) received the prescribed clinical dose of 1200 mg/kg NAC which reverses the hepatotoxicity. All the NAC doses were given once a day intragastric for 7 days. On days: 1, 3 and 7 of receiving NAC, liver serum enzymes and bilirubin were measured. On day 7 the animals were sacrificed and liver tissue harvested for histopathology analysis. Results: A dose of 8.05 g/kg of M. oleifera leaf extract and 0.75 mg/kg Paracetamol were able to induce hepatotoxicity in Wister albino rats in 28 days. The M. oleifera extract induced hepatotoxic rats treated with NAC at doses of 1000 mg/kg, 1200 mg/kg and 1500 mg/kg, had a reduction in mean serum liver enzymes, plus reduced mean serum bilirubin levels. The liver histopathological analysis showed reduced inflammation after treatment with NAC for 3 and 7 days in the M. oleifera and paracetamol induced hepatotoxic rats. Conclusion: NAC can reverse M. oleifera leaf aqueous extract-induced sub-acute hepatotoxicity in Wistar Albino rats.展开更多
Objective: To determine the toxicity of Sapium ellipticum (S. ellipticum) ethanol leaf extract in animal model. Methods: Three groups (Ⅰ, Ⅱ and Ⅲ, n = 10) of Wistar rats were respectively given 0.5 mL corn oil, 400...Objective: To determine the toxicity of Sapium ellipticum (S. ellipticum) ethanol leaf extract in animal model. Methods: Three groups (Ⅰ, Ⅱ and Ⅲ, n = 10) of Wistar rats were respectively given 0.5 mL corn oil, 400 and 800 mg/kg BW of S. ellipticum extract, twice daily, for a period of 14 days. Lethal dose (LD50) was determined and morbidity was assessed via repeated dose administration of the extract. Results: S. ellipticum at the doses employed did not cause any significant changes in the serum concentrations of ALT, AST and ALP compared to the control group. The level of total serum cholesterol was significantly (P < 0.05) and dose-dependently reduced in the extract-treated animals by 13.5% and 16.0% compared to the control animals. Total plasma protein concentration and body weight were respectively increased by 8.7% and 13.7% at 800 mg dosage of the extract. The intraperitoneal (i.p.) and intramuscular (i.m.) LD50 values of S. ellipticum leaf extract were determined as 979.80 and 1341.60 mg/kg BW respectively while the oral (p.o.) LD50 was estimated to be greater than 45000 mg/kg BW. Conclusions: The observations noted in this study apparently validate the use of S. ellipticum ethanol leaf extract in folklore medicine in terms of herbal safety.展开更多
Objective:To assess the potential toxicity of hydroalcoholic extract of Allium affine(A.affine)aerial parts after acute and sub-acute administration in female and male Wistar rats.Methods:For acute toxicity assay,anim...Objective:To assess the potential toxicity of hydroalcoholic extract of Allium affine(A.affine)aerial parts after acute and sub-acute administration in female and male Wistar rats.Methods:For acute toxicity assay,animals orally received the limit test dose of 2000 mg/kg of A.affine extract and were observed for 2 weeks.For sub-acute toxicity study,rats were orally treated with 125,250,and 500 mg/kg/day of the extract over 28 days,and hematological,biochemical,and histological evaluations were then conducted.Results:All rats were alive with normal body weight gain over 14 days,with LD50˃2000 mg/kg.No abnormality in body weight changes but significant increases in the relative weight of spleen and lung were detected after administration of the highest dose of extract for 28 days in sub-acute assay.Hematological analysis showed prominent elevations in total white blood cells in male rats and neutrophils count in female rats after exposure to 500 mg/kg of A.affine extract.In biochemical evaluations,significant increases in serum creatinine level(female rats,250 and 500 mg/kg)and in aspartate aminotransferase(male and female rate,500 mg/kg)and alanine aminotransferase(male,250 and 500 mg/kg and female,500 mg/kg)activities,however,notable decreases in serum blood glucose(male rats,125 and 500 mg/kg),triglycerides(male rats,500 mg/kg and female rates,250 mg/kg),and low-density lipoprotein cholesterol levels(male,250 mg/kg)were found.Histological examinations presented slight portal inflammation in liver tissue,moderate pneumocyte hyperplasia,congestion and peri-bronchial inflammation in lung tissue,and mild histiocytosis and lymphoid follicular activation in spleen tissue after exposure to 500 mg/kg of A.affine extract in male and female animals.Conclusions:The present investigation reveals the safety of A.affine extract at doses of lower than 250 mg/kg in rats and monitoring of lung,spleen,and liver functions is suggested during excessive and prolonged uses.展开更多
Momordica foetida is a plant widely used in tropical Africa to manage gastroenteric diseases. Previous studies demonstrated interesting antibacterial activity against human pathogenic bacteria. However, the security o...Momordica foetida is a plant widely used in tropical Africa to manage gastroenteric diseases. Previous studies demonstrated interesting antibacterial activity against human pathogenic bacteria. However, the security or toxicity of methanol leaf extract has not been determined yet. The aim of this study was to evaluate the acute and sub-acute toxicity of the leaf extract of Momordica foetida. In the acute toxicity study, a single oral dose of 5000 mg/kg body weight was administered to rats which were observed for 14 days in order to identify signs of toxicity or death. In the sub-acute toxicity, the animals were treated with 250, 500 and 1000 mg/kg of the extract for 28 consecutive days. Body weights and behavior were noted throughout the experiment. Upon treatment, blood and urine were collected for hematological and biochemical analysis. Liver, lungs, heart, kidneys, testes and ovaries were analyzed for relative weights and histopathology. The acute toxicity study of M. foetida leaf extract revealed no signs of toxicity related to the treatment, indicating that the median-lethal-dose (LD50) value is greater than 5000 mg/Kg of body weight. In the sub-acute toxicity assay, the extract did not affect the general behavior of animals, meanwhile, it led to a significant increase in the levels of red blood cells, platelets, hemoglobin, granulocytes and Mid-Cells (MIDs). Biochemical parameters showed an increase in total cholesterol, HDL cholesterol, serum urea, serum and urinary glucose and a decrease in urinary proteins, serum creatinine, urinary urea levels, serum activities of AST, ALT and proteins levels, as well as increases in lung, spleen and ovaries relative weight were noticed, all compared to control animals. Histological analysis revealed a normal architecture of kidneys, liver, heart, lung, ovaries and testes. This study provides valuable data on the safety of per os administration of Momordica foetida leaf methanol extract that could be very useful for future assays.展开更多
Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.Howeve...Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.展开更多
Peptide-based therapeutics hold great promise for the treatment of various diseases;however,their clinical application is often hindered by toxicity challenges.The accurate prediction of peptide toxicity is crucial fo...Peptide-based therapeutics hold great promise for the treatment of various diseases;however,their clinical application is often hindered by toxicity challenges.The accurate prediction of peptide toxicity is crucial for designing safe peptide-based therapeutics.While traditional experimental approaches are time-consuming and expensive,computational methods have emerged as viable alternatives,including similarity-based and machine learning(ML)-/deep learning(DL)-based methods.However,existing methods often struggle with robustness and generalizability.To address these challenges,we propose HyPepTox-Fuse,a novel framework that fuses protein language model(PLM)-based embeddings with conventional descriptors.HyPepTox-Fuse integrates ensemble PLM-based embeddings to achieve richer peptide representations by leveraging a cross-modal multi-head attention mechanism and Transformer architecture.A robust feature ranking and selection pipeline further refines conventional descriptors,thus enhancing prediction performance.Our framework outperforms state-of-the-art methods in cross-validation and independent evaluations,offering a scalable and reliable tool for peptide toxicity prediction.Moreover,we conducted a case study to validate the robustness and generalizability of HyPepTox-Fuse,highlighting its effectiveness in enhancing model performance.Furthermore,the HyPepTox-Fuse server is freely accessible at https://balalab-skku.org/HyPepTox-Fuse/and the source code is publicly available at https://github.com/cbbl-skku-org/HyPepTox-Fuse/.The study thus presents an intuitive platform for predicting peptide toxicity and supports reproducibility through openly available datasets.展开更多
BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their...BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.展开更多
The herbal drink “Attoté” has been widely used in the Abidjan district to treat a number of illnesses, notably erectile dysfunction. Despite the popularity of its therapeutic effects, very few studies have been...The herbal drink “Attoté” has been widely used in the Abidjan district to treat a number of illnesses, notably erectile dysfunction. Despite the popularity of its therapeutic effects, very few studies have been carried out on its effects on the health of users. The aim of this study was to identify the constituents contained in the phytomedicinal product and to assess their potential adverse effects in vivo. Phytochemical screening was conducted to identify the bioactive molecules in “Attoté” and to evaluate its hepatic effects in vivo. Forty (40) Wistar rats, randomly divided into 4 groups, with 10 animals per group (5 males and 5 females) were used to study potential hepatotoxic effects. Group 1 animals (control group) received distilled water. Batches I, II and III received by gavage a volume of Attoté extract corresponding to 1 ml/100 g body weight at 200 mg/kg, 400 mg/kg and 800 mg/kg, respectively. Attoté extract was administered daily at the same time for 28 days, and serum was collected every two weeks to assess hepatic biochemical markers by spectrophotometry using a Cobas C311® HITACHI biochemistry system. After one month of study, the rats were euthanized by ether overdose and the livers were harvested for morphological and histopathological analysis. Phytochemical screening revealed the presence of alkaloids, polyphenols, leucoanthocyanes, anthraquinones and quinones. Hepatic biochemical and hematological parameters such as red globular, hemoglobin, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALPs) and gamma glutamyl transferase (GGT) showed no significant change (p > 0.05) in the treated rat group compared with controls. However, these variations were moderate and transient, with values remaining almost within their standard limits. Microscopic observations of liver tissue sections from treated rats showed no liver damage or dysfunction. This study merits further investigation, with a view to gaining a better understanding of the cytotoxic mechanisms of herbal medicinal beverages, with a view to their reformulation as improved traditional medicines (ITMs).展开更多
Developmental and reproductive toxicity(DART)endpoint entails a toxicological assessment of all developmental stages and reproductive cycles of an organism.In silico tools to predict DART will provide a method to asse...Developmental and reproductive toxicity(DART)endpoint entails a toxicological assessment of all developmental stages and reproductive cycles of an organism.In silico tools to predict DART will provide a method to assess this complex toxicity endpoint and will be valuable for screening emerging pollutants as well as for m anaging new chemicals in China.Currently,there are few published DART prediction models in China,but many related research and development projects are in progress.In 2013,WU et al.published an expert rule-based DART decision tree(DT).This DT relies on known chemical structures linked to DART to forecast DART potential of a given chemical.Within this procedure,an accurate DART data interpretation is the foundation of building and expanding the DT.This paper excerpted case studies demonstrating DART data curation and interpretation of four chemicals(including 8-hydroxyquinoline,3,5,6-trichloro-2-pyridinol,thiacloprid,and imidacloprid)to expand the existing DART DT.Chemicals were first selected from the database of Solid Waste and Chemicals Management Center,Ministry of Ecology and Environment(MEESCC)in China.The structures of these 4 chemicals were analyzed and preliminarily grouped by chemists based on core structural features,functional groups,receptor binding property,metabolism,and possible mode of actions.Then,the DART conclusion was derived by collecting chemical information,searching,integrating,and interpreting DART data by the toxicologists.Finally,these chemicals were classified into either an existing category or a new category via integrating their chemical features,DART conclusions,and biological properties.The results showed that 8-hydroxyquinoline impacted estrous cyclicity,s exual organ weights,and embryonal development,and 3,5,6-trichloro-2-pyridinol caused central nervous system(CNS)malformations,which were added to an existing subcategory 8e(aromatic compounds with multi-halogen and nitro groups)of the DT.Thiacloprid caused dystocia and fetal skeletal malformation,and imidacloprid disrupted the endocrine system and male fertility.They both contain 2-chloro-5-methylpyridine substituted imidazolidine c yclic ring,which were expected to create a new category of neonicotinoids.The current work delineates a t ransparent process of curating toxicological data for the purpose of DART data interpretation.In the presence of sufficient related structures and DART data,the DT can be expanded by iteratively adding chemicals within the a pplicable domain of each category or subcategory.This DT can potentially serve as a tool for screening emerging pollutants and assessing new chemicals in China.展开更多
The extensive co-occurrence of pyrethroid insecticides such as lambda-cyhalothrin(LCT)and cypermethrin(CPM)in aquatic systems poses a potential risk,yet a significant research gap exists regarding their combined toxic...The extensive co-occurrence of pyrethroid insecticides such as lambda-cyhalothrin(LCT)and cypermethrin(CPM)in aquatic systems poses a potential risk,yet a significant research gap exists regarding their combined toxicological effects.In this study,the single and joint acute toxicity effects of lambda-cyhalothrin(LCT)and cypermethrin(CPM)on Nile tilapia fingerlings were investigated using 96-h bioassays.Results showed both were highly toxic,with LCT(96-h LC 50=66.53μg/L)being four-fold more potent than CPM(259.41μg/L).Regression analysis confirmed positive correlation(P<0.01)between pesticide concentration and observed mortality.The binary mixture exhibited synergistic effect with Additive Index(AI)>0,indicating combined effects exceeded the sum of their individual actions.This synergism likely stems from mutual inhibition of metabolic detoxification pathways,leading to increased internal concentrations and amplified neurotoxicity.Generally,this study confirmed that single-compound risk assessments dangerously underestimate pyrethroid mixture hazards,necessitating their inclusion in regulatory frameworks for accurate aquatic biodiversity protection.展开更多
In this study,the single and jiont acute toxicity effects of pendimethalin(herbicide)and fenitrothion(organophosphate insecticide)were investigated on juvenile zebrafish(Danio rerio)under semi-static conditions.Mortal...In this study,the single and jiont acute toxicity effects of pendimethalin(herbicide)and fenitrothion(organophosphate insecticide)were investigated on juvenile zebrafish(Danio rerio)under semi-static conditions.Mortality was assessed at 24,48,72,and 96 h.The study revealed that pendimethalin exhibited higher toxicity than fenitrothion.The 96-h LC 50 values were 0.477 mg/L for pendimethalin and 2.634 mg/L for fenitrothion.Joint exposure produced enhanced toxicity,with 96-h LC 50 values of 0.204 mg/L(pendimethalin equivalent)and 1.139 mg/L(fenitrothion equivalent).Regression analysis showed a significant positive correlation(p<0.05)between pesticide concentration and mortality,while toxicity indices confirmed synergistic interactions.These findings underscore the ecological risks posed by pesticide mixtures and highlight the importance of regulating pesticide use to safeguard aquatic organisms and maintain environmental sustainability.展开更多
This study attempted to assess the lethal concentration(96-h LC_(50))effects of imidacloprid(neonicotinoid pesticide),thiamethoxam(neonicotinoid pesticide),and their combination on juvenile Zebrafish(Danio rerio).Each...This study attempted to assess the lethal concentration(96-h LC_(50))effects of imidacloprid(neonicotinoid pesticide),thiamethoxam(neonicotinoid pesticide),and their combination on juvenile Zebrafish(Danio rerio).Each set of trials contained a control(de-chlorinated tap water),and the experiments were repeated three times.The fish(n=10)were randomly measured with an average length of(3.4±0.34)cm and weight of(1±0.1)g.The temperature was kept at 24℃.Experiments 1 and 2 were designed to investigate at the acute toxicity of imidacloprid and thiamethoxam on juvenile zebrafish(Danio rerio)respectively,whereas experiment 3 was aimed at the combined toxicity of IMI and THM on zebrafish.The tests followed the same study design,and each experiment used seven different logarithmic concentrations of imidacloprid insecticides(310.00,317.08,324.33,331.74,339.32,347.07,355.00 mg/L)and thiamethoxam(175.00,185.52,200.93,215.30,230.70,247.20,264.88 mg/L).The results show that THM is more toxic than IMI,with LC_(50)values of 190.34 mg/L for THM and 310.92 mg/L for IMI.Both individual toxicities showed a substantial positive connection(P<0.05)with confidence limits of 321.50-300.68 mg/L for IMI and 199.91-181.21 mg/L for THM.The joint toxicity test was carried out using the 96-h LC_(50)values of imidacloprid and thiamethoxam obtained in the individual acute toxicity trials at a 1:1 ratio.The Additive Index(AI)demonstrated that imidacloprid and thiamethoxam acted synergistically on D.rerio.As a matter of fact,more research is needed to better understand the impact of IMI and THM on other aquatic organisms and also create strategies to mitigate its harmful effects on aquatic life.展开更多
Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration tec...Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration technique,where the test substance is suspended in a liquid vehicle and deposited into the lung via the trachea.Instillation requires minimal test material,delivers an exact dose deep into the lung,and is less labor-intensive than inhalation exposures.However,one shortcoming is that the pro-cedure may induce short-term inflammation.To minimize this,we tested different modifications of the technique to identify the potential for refinement.Methods:First,we tested whether previous findings of increased inflammation could be confirmed.Next,we tested whether instillation with a disposable 1 mL syringe with ball-tipped steel-needle(Disposable-syringe/steel-needle)induced less inflammation than the use of our standard set-up,a 250μL reusable glass syringe with a disposable plastic catheter(Glass-syringe/plastic-catheter).Finally,we tested if access to pelleted and liquid feed prior to instillation affected inflammation.We evaluated inflammation by neutrophil numbers in bronchoalveolar fluid 24 h post-exposure.Results:Vehicle-instilled mice showed a small increase in neutrophil numbers com-pared to untreated mice.Neutrophil numbers were slightly elevated in the groups in-stilled with Disposable-syringe/steel-needle;an interaction with feed type indicated that the increase in neutrophils was more pronounced in combination with feed pel-lets compared to liquid feed.We found no difference between the feed types when using the Glass-syringe/plastic-catheter combination.Conclusion:The Glass-syringe/plastic-catheter combination induced the least exposure-related inflammation,confirming this as a preferred instillation procedure.展开更多
To evaluate the subchronic and chronic toxicity of Fuyanxiao capsules,Sprague-Dawley(SD)rats were used in toxicity studies.In the subchronic toxicity study,50 female rats were randomly divided into a high-dose group(5...To evaluate the subchronic and chronic toxicity of Fuyanxiao capsules,Sprague-Dawley(SD)rats were used in toxicity studies.In the subchronic toxicity study,50 female rats were randomly divided into a high-dose group(5.4g/kg/day)and a control group,with 15 rats in each,and medium(2.7g/kg/day)and low(1.35g/kg/day)dose groups,with 10 rats in each.The test substance was administered orally(mixed with feed,twice daily)for 90 consecutive days.In the chronic toxicity study,40 female rats were randomly divided into high,medium,and low dose groups and a control group,with 10 rats in each.The test substance was administered orally in the same manner for 180 consecutive days.Clinical signs,body weight,and food consumption were observed and recorded daily.At the end of the terminal phase(the first 10 rats from each group,1 day after the last dose)and the recovery phase(the last 5 rats from the control group and the high-dose group,observed for an additional 28 days after the last dose),blood and urine samples,as well as organs,were collected.Organ coefficients were calculated,and various hematological and urinary indicators were detected,followed by pathological analysis.The results showed that there were no significant differences in body weight,food consumption,or organ coefficients between any of the dose groups and the control group in both subchronic and chronic toxicity studies(P>0.05).Histopathological examination revealed no lesions,suggesting no tissue or organ damage in any of the dose groups.The rats exhibited good mental status,and hematological and urinary physiological indicators were within normal ranges,indicating stable liver and kidney function,hematopoietic system of the bone marrow,and internal environment in all dose groups.Therefore,Fuyanxiao capsule has no obvious subchronic or chronic toxicity in SD rats,and it is safe and reliable to use at reasonable dosage in clinical practice.展开更多
文摘To explore the toxicological profile of methanol extract of Chlorophytum alismifolium (MECA) tubers in Wistar rats. Methods: MECA was subjected to acute and sub-acute studies which were conducted according to Organization for Economic Co-operation and Development (OECD 425 and 407 guidelines respectively). In the acute toxicity experiment, a limit test (5000 mg/kg) was administered to five rats and monitored for 2 weeks. The sub-acute studies were conducted on 4 groups of rats. The first group served as control, while the 2nd, 3rd and 4th groups received MECA (150, 300 and 600 mg/kg respectively). The treatments were given orally and daily for 4 weeks. At the end of the experiment (29th day), the animals were euthanized to obtain blood samples and organs for haematological, biochemical and histological evaluations. Results: Acute toxicity study showed that the oral median lethal dose was >5000 mg/kg. In the sub-acute studies, the results showed no significant (P>0.05) changes in the haematological, hepatic and renal indices compared to control animals. In the fourth week, a significant (P<0.01) increase in body weight of the rats was observed at 150 mg/kg and 600 mg/kg compared to week one. However, there were no major changes in the organ/body weights of the rats. Histological examination of the kidney showed slight glomerular adhesion and tubular distortion. Moderate hepatic necrosis was observed at 150 mg/kg and 300 mg/kg. Conclusions: The results of this research revealed that the MECA tubers is virtually non-toxic after acute administration and it has low sub-acute toxicity potential in rats.
文摘Rumex abyssinica Jacq. (Polygonaceae) is locally used in management of allergies and female reproductive healthcare;whereas Mentha spicata L. (Lamiaceae) is used to treat gastrointestinal and respiratory distress, dandruff, halitosis and malaria in Uganda. Owing to the paucity of data on their safety profiles, this study evaluated the acute and sub-acute toxicities of 70% ethanolic leaf extracts of both plants in mice and Wistar albino rats. The oral acute toxicity of both plants was evaluated in Swiss mice of 7-8 weeks old (16-22 g) body weight and LD50 determined. Sub-acute toxicity was evaluated in Wistar albino rats (6 per group) at dose rates of 500, 1000 and 1500 mg/kg for 28 days. The LD50 of R. abyssinica and M. spicata in mice was 7727 mg/kg and 13,606 mg/kg body weight, respectively. General signs of toxicity due to large doses of both plants extract included hyperurination, abdominal muscle twitches and convulsions. In the sub-acute toxicity test, rats treated with both extracts did not exhibit any clinical signs of toxicity;no mortality and changes in body weight were observed. R. abyssinica did not cause significant changes in haematological indices, except a significant increase in HCT (p 0.05). However, a dose dependant significant decrease in HCT (p 0.05) and a significant increase (p 0.05) in the levels of WBC, LMY and MCHC were observed in rats treated with M. spicata extract. Biochemical test showed that both extracts caused a significant dose dependent increase (p 0.05) in levels of ALT and ALP. Marked increase in the levels of AST was also observed in rats treated with M. spicata extract. Of the two extracts, only rats treated with </
文摘The inhibition of acetylcholinesterase (ACHE) activity has been widely used as a biomarker in an animal exposed to the pesticides. However, the interaction of extensively used organocarbamate insecticide, carbofuran, with the nervous system of the aquatic organisms is not properly studied. AChE is a key enzyme which catalyses the hydrolysis of acetylcholine, a neurotransmitter at the neuromuscular junctions, and thus regulates the neurotransmission system. In the present study, we have evaluated the impact of sub-acute concentrations (0.01 and 0.02 mg/L i.e. 1/20th and 1/10th of LC50) of carbofuran on the activity of acetylcholinesterase,from different tissues of Clarias batrachus, a fresh water teleost, after 96 hr and 15 days exposure periods in vivo. The carbofuran significantly reduced the activity of AChE in different tissues of C. batrachus at both concentrations and periods of exposure. The greater inhibition of AChE activities were recorded in fish tissues at higher carbofuran concentration (0.02 mg/L) after longer (15days) treatment period. The inhibition of AChE activity in all fish tissues tested was dependent on pesticide concentration and the duration of treatment. AChE from the tissues of C. batrachus was found to be a true cholinesterase as it was completely inhibited by the small concentration (nM) of eserine as tested in vitro. It was found that carbofuran at very low concentration exerted significant inhibitory effect on AChE activity in fish tissues.
文摘AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.
基金funded by The Tunisian Ministry of Research and Higher Education.
文摘Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.
基金supported by grants from the National Natural Science Foundation of China(No.81030053)the Doctoral Foundation of the Chinese Ministry of Education(No.20120181110040)
文摘No data were available on the acute oral toxicity, short-term oral toxicity of vegetable carbon in animals. This study was designed to evaluate the safety of two commercially available dietary bamboo charcoal powders（BCP1 and BCP2）. The size distribution of the two powders was determined by a Mastersizer 2000 laser particle size analyzer prior to the in vivo safety studies. For the acute toxicity study, a single dose of 11.24 g/kg body weight of BCP1 and BCP2 was given once orally to healthy Sprague-Dawley（SD） rats. Mortality and clinical symptoms were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. In the repeated dose 28-day oral toxicity study, BCP1 and BCP2 were administered orally at doses of 2.81, 5.62, and 11.24 g/kg body weight for 28 days to SD rats. Animals were sacrificed and organs and blood samples were analyzed. Results showed that both BCP1 and BCP2 were micro-sized and various in size. In the acute toxicity and the repeated dose 28-day oral toxicity studies, BCP caused neither mortality nor visible signs of toxicity in rats. No significant differences were found in the relative organ weights or in biochemical parameters in BCP treated groups compared to a control group. No treatment-related histological changes were observed in the organs of these animals. Based on these data, it is concluded that the median lethal dose（LD50） of BCP for both male and female rats is more than 11. 24 g/kg body weight and the no-observed-adverse-effect level（NOAEL） is 〉11.24 g/kg body weight for 28 days.
文摘Background: M. oleifera is a highly valued medicinal plant used widely from time immemorial to treat various ailments. However, with continued un-standardized use of the plant leaves, studies have reported organ toxicity to the liver, kidney and the heart. As communities continue to use M. oleifera leaves for its medicinal and nutritional values, there is need to find an antidote for its hepatotoxicity. Aim: The study established the reversal effect of N-Acetyl Cysteine (NAC) on M. oleifera aqueous leaf extract-induced hepatotoxicity in Wistar albino rats. Methods: Twenty-four (24) rats received a toxic dose (8.05 g/kg bwt) of M. oleifera leaf extract for 28 days to cause sub-acute hepatotoxicity. They were divided into 4 groups of 6 rats each. Group I received 1 ml normal (control group), Group II received 1000 ng/kg NAC, Group III received 1200 mg/kg NAC and Group IV received 1500 mg/kg NAC. Another group of 6 rats (Group V) received 0.75 mg/kg Paracetamol to cause hepatotoxicity. Group V (a positive control) received the prescribed clinical dose of 1200 mg/kg NAC which reverses the hepatotoxicity. All the NAC doses were given once a day intragastric for 7 days. On days: 1, 3 and 7 of receiving NAC, liver serum enzymes and bilirubin were measured. On day 7 the animals were sacrificed and liver tissue harvested for histopathology analysis. Results: A dose of 8.05 g/kg of M. oleifera leaf extract and 0.75 mg/kg Paracetamol were able to induce hepatotoxicity in Wister albino rats in 28 days. The M. oleifera extract induced hepatotoxic rats treated with NAC at doses of 1000 mg/kg, 1200 mg/kg and 1500 mg/kg, had a reduction in mean serum liver enzymes, plus reduced mean serum bilirubin levels. The liver histopathological analysis showed reduced inflammation after treatment with NAC for 3 and 7 days in the M. oleifera and paracetamol induced hepatotoxic rats. Conclusion: NAC can reverse M. oleifera leaf aqueous extract-induced sub-acute hepatotoxicity in Wistar Albino rats.
文摘Objective: To determine the toxicity of Sapium ellipticum (S. ellipticum) ethanol leaf extract in animal model. Methods: Three groups (Ⅰ, Ⅱ and Ⅲ, n = 10) of Wistar rats were respectively given 0.5 mL corn oil, 400 and 800 mg/kg BW of S. ellipticum extract, twice daily, for a period of 14 days. Lethal dose (LD50) was determined and morbidity was assessed via repeated dose administration of the extract. Results: S. ellipticum at the doses employed did not cause any significant changes in the serum concentrations of ALT, AST and ALP compared to the control group. The level of total serum cholesterol was significantly (P < 0.05) and dose-dependently reduced in the extract-treated animals by 13.5% and 16.0% compared to the control animals. Total plasma protein concentration and body weight were respectively increased by 8.7% and 13.7% at 800 mg dosage of the extract. The intraperitoneal (i.p.) and intramuscular (i.m.) LD50 values of S. ellipticum leaf extract were determined as 979.80 and 1341.60 mg/kg BW respectively while the oral (p.o.) LD50 was estimated to be greater than 45000 mg/kg BW. Conclusions: The observations noted in this study apparently validate the use of S. ellipticum ethanol leaf extract in folklore medicine in terms of herbal safety.
基金financially supported by Vice-Chancellery for Research and Technology,Isfahan University of Medical Sciences(Grant No.399187).
文摘Objective:To assess the potential toxicity of hydroalcoholic extract of Allium affine(A.affine)aerial parts after acute and sub-acute administration in female and male Wistar rats.Methods:For acute toxicity assay,animals orally received the limit test dose of 2000 mg/kg of A.affine extract and were observed for 2 weeks.For sub-acute toxicity study,rats were orally treated with 125,250,and 500 mg/kg/day of the extract over 28 days,and hematological,biochemical,and histological evaluations were then conducted.Results:All rats were alive with normal body weight gain over 14 days,with LD50˃2000 mg/kg.No abnormality in body weight changes but significant increases in the relative weight of spleen and lung were detected after administration of the highest dose of extract for 28 days in sub-acute assay.Hematological analysis showed prominent elevations in total white blood cells in male rats and neutrophils count in female rats after exposure to 500 mg/kg of A.affine extract.In biochemical evaluations,significant increases in serum creatinine level(female rats,250 and 500 mg/kg)and in aspartate aminotransferase(male and female rate,500 mg/kg)and alanine aminotransferase(male,250 and 500 mg/kg and female,500 mg/kg)activities,however,notable decreases in serum blood glucose(male rats,125 and 500 mg/kg),triglycerides(male rats,500 mg/kg and female rates,250 mg/kg),and low-density lipoprotein cholesterol levels(male,250 mg/kg)were found.Histological examinations presented slight portal inflammation in liver tissue,moderate pneumocyte hyperplasia,congestion and peri-bronchial inflammation in lung tissue,and mild histiocytosis and lymphoid follicular activation in spleen tissue after exposure to 500 mg/kg of A.affine extract in male and female animals.Conclusions:The present investigation reveals the safety of A.affine extract at doses of lower than 250 mg/kg in rats and monitoring of lung,spleen,and liver functions is suggested during excessive and prolonged uses.
文摘Momordica foetida is a plant widely used in tropical Africa to manage gastroenteric diseases. Previous studies demonstrated interesting antibacterial activity against human pathogenic bacteria. However, the security or toxicity of methanol leaf extract has not been determined yet. The aim of this study was to evaluate the acute and sub-acute toxicity of the leaf extract of Momordica foetida. In the acute toxicity study, a single oral dose of 5000 mg/kg body weight was administered to rats which were observed for 14 days in order to identify signs of toxicity or death. In the sub-acute toxicity, the animals were treated with 250, 500 and 1000 mg/kg of the extract for 28 consecutive days. Body weights and behavior were noted throughout the experiment. Upon treatment, blood and urine were collected for hematological and biochemical analysis. Liver, lungs, heart, kidneys, testes and ovaries were analyzed for relative weights and histopathology. The acute toxicity study of M. foetida leaf extract revealed no signs of toxicity related to the treatment, indicating that the median-lethal-dose (LD50) value is greater than 5000 mg/Kg of body weight. In the sub-acute toxicity assay, the extract did not affect the general behavior of animals, meanwhile, it led to a significant increase in the levels of red blood cells, platelets, hemoglobin, granulocytes and Mid-Cells (MIDs). Biochemical parameters showed an increase in total cholesterol, HDL cholesterol, serum urea, serum and urinary glucose and a decrease in urinary proteins, serum creatinine, urinary urea levels, serum activities of AST, ALT and proteins levels, as well as increases in lung, spleen and ovaries relative weight were noticed, all compared to control animals. Histological analysis revealed a normal architecture of kidneys, liver, heart, lung, ovaries and testes. This study provides valuable data on the safety of per os administration of Momordica foetida leaf methanol extract that could be very useful for future assays.
基金supported by the Guangdong Provincial Key Area Research and Development Program[grant number 2022B0202090002]China Postdoctoral Science Foundation[grant number 2024M760977].
文摘Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.
基金supported by the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT,Republic of Korea(Grant No.:RS-2024-00344752)supported by the Department of Integrative Biotechnology,Sungkyunkwan University(SKKU)and the BK21 FOUR Project,Republic of Korea.
文摘Peptide-based therapeutics hold great promise for the treatment of various diseases;however,their clinical application is often hindered by toxicity challenges.The accurate prediction of peptide toxicity is crucial for designing safe peptide-based therapeutics.While traditional experimental approaches are time-consuming and expensive,computational methods have emerged as viable alternatives,including similarity-based and machine learning(ML)-/deep learning(DL)-based methods.However,existing methods often struggle with robustness and generalizability.To address these challenges,we propose HyPepTox-Fuse,a novel framework that fuses protein language model(PLM)-based embeddings with conventional descriptors.HyPepTox-Fuse integrates ensemble PLM-based embeddings to achieve richer peptide representations by leveraging a cross-modal multi-head attention mechanism and Transformer architecture.A robust feature ranking and selection pipeline further refines conventional descriptors,thus enhancing prediction performance.Our framework outperforms state-of-the-art methods in cross-validation and independent evaluations,offering a scalable and reliable tool for peptide toxicity prediction.Moreover,we conducted a case study to validate the robustness and generalizability of HyPepTox-Fuse,highlighting its effectiveness in enhancing model performance.Furthermore,the HyPepTox-Fuse server is freely accessible at https://balalab-skku.org/HyPepTox-Fuse/and the source code is publicly available at https://github.com/cbbl-skku-org/HyPepTox-Fuse/.The study thus presents an intuitive platform for predicting peptide toxicity and supports reproducibility through openly available datasets.
基金Supported by the Chongqing Medical University Program for Youth Innovation in Future Medicine,No.W0019Chongqing Municipal Education Commission’s 14th Five-Year Key Discipline Support Project,No.20240101 and No.20240102。
文摘BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.
文摘The herbal drink “Attoté” has been widely used in the Abidjan district to treat a number of illnesses, notably erectile dysfunction. Despite the popularity of its therapeutic effects, very few studies have been carried out on its effects on the health of users. The aim of this study was to identify the constituents contained in the phytomedicinal product and to assess their potential adverse effects in vivo. Phytochemical screening was conducted to identify the bioactive molecules in “Attoté” and to evaluate its hepatic effects in vivo. Forty (40) Wistar rats, randomly divided into 4 groups, with 10 animals per group (5 males and 5 females) were used to study potential hepatotoxic effects. Group 1 animals (control group) received distilled water. Batches I, II and III received by gavage a volume of Attoté extract corresponding to 1 ml/100 g body weight at 200 mg/kg, 400 mg/kg and 800 mg/kg, respectively. Attoté extract was administered daily at the same time for 28 days, and serum was collected every two weeks to assess hepatic biochemical markers by spectrophotometry using a Cobas C311® HITACHI biochemistry system. After one month of study, the rats were euthanized by ether overdose and the livers were harvested for morphological and histopathological analysis. Phytochemical screening revealed the presence of alkaloids, polyphenols, leucoanthocyanes, anthraquinones and quinones. Hepatic biochemical and hematological parameters such as red globular, hemoglobin, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALPs) and gamma glutamyl transferase (GGT) showed no significant change (p > 0.05) in the treated rat group compared with controls. However, these variations were moderate and transient, with values remaining almost within their standard limits. Microscopic observations of liver tissue sections from treated rats showed no liver damage or dysfunction. This study merits further investigation, with a view to gaining a better understanding of the cytotoxic mechanisms of herbal medicinal beverages, with a view to their reformulation as improved traditional medicines (ITMs).
文摘Developmental and reproductive toxicity(DART)endpoint entails a toxicological assessment of all developmental stages and reproductive cycles of an organism.In silico tools to predict DART will provide a method to assess this complex toxicity endpoint and will be valuable for screening emerging pollutants as well as for m anaging new chemicals in China.Currently,there are few published DART prediction models in China,but many related research and development projects are in progress.In 2013,WU et al.published an expert rule-based DART decision tree(DT).This DT relies on known chemical structures linked to DART to forecast DART potential of a given chemical.Within this procedure,an accurate DART data interpretation is the foundation of building and expanding the DT.This paper excerpted case studies demonstrating DART data curation and interpretation of four chemicals(including 8-hydroxyquinoline,3,5,6-trichloro-2-pyridinol,thiacloprid,and imidacloprid)to expand the existing DART DT.Chemicals were first selected from the database of Solid Waste and Chemicals Management Center,Ministry of Ecology and Environment(MEESCC)in China.The structures of these 4 chemicals were analyzed and preliminarily grouped by chemists based on core structural features,functional groups,receptor binding property,metabolism,and possible mode of actions.Then,the DART conclusion was derived by collecting chemical information,searching,integrating,and interpreting DART data by the toxicologists.Finally,these chemicals were classified into either an existing category or a new category via integrating their chemical features,DART conclusions,and biological properties.The results showed that 8-hydroxyquinoline impacted estrous cyclicity,s exual organ weights,and embryonal development,and 3,5,6-trichloro-2-pyridinol caused central nervous system(CNS)malformations,which were added to an existing subcategory 8e(aromatic compounds with multi-halogen and nitro groups)of the DT.Thiacloprid caused dystocia and fetal skeletal malformation,and imidacloprid disrupted the endocrine system and male fertility.They both contain 2-chloro-5-methylpyridine substituted imidazolidine c yclic ring,which were expected to create a new category of neonicotinoids.The current work delineates a t ransparent process of curating toxicological data for the purpose of DART data interpretation.In the presence of sufficient related structures and DART data,the DT can be expanded by iteratively adding chemicals within the a pplicable domain of each category or subcategory.This DT can potentially serve as a tool for screening emerging pollutants and assessing new chemicals in China.
基金Supported by The Central Public-Interest Scientific Institution Basal Research Fund,CAFS(2025XT0902)Earmarked Fund for China Agriculture Research System(CARS-46).
文摘The extensive co-occurrence of pyrethroid insecticides such as lambda-cyhalothrin(LCT)and cypermethrin(CPM)in aquatic systems poses a potential risk,yet a significant research gap exists regarding their combined toxicological effects.In this study,the single and joint acute toxicity effects of lambda-cyhalothrin(LCT)and cypermethrin(CPM)on Nile tilapia fingerlings were investigated using 96-h bioassays.Results showed both were highly toxic,with LCT(96-h LC 50=66.53μg/L)being four-fold more potent than CPM(259.41μg/L).Regression analysis confirmed positive correlation(P<0.01)between pesticide concentration and observed mortality.The binary mixture exhibited synergistic effect with Additive Index(AI)>0,indicating combined effects exceeded the sum of their individual actions.This synergism likely stems from mutual inhibition of metabolic detoxification pathways,leading to increased internal concentrations and amplified neurotoxicity.Generally,this study confirmed that single-compound risk assessments dangerously underestimate pyrethroid mixture hazards,necessitating their inclusion in regulatory frameworks for accurate aquatic biodiversity protection.
基金Supported by The Central Public-Interest Scientific Institution Basal Research Fund,CAFS(2025XT0902)Earmarked Fund for China Agriculture Research System(CARS-46).
文摘In this study,the single and jiont acute toxicity effects of pendimethalin(herbicide)and fenitrothion(organophosphate insecticide)were investigated on juvenile zebrafish(Danio rerio)under semi-static conditions.Mortality was assessed at 24,48,72,and 96 h.The study revealed that pendimethalin exhibited higher toxicity than fenitrothion.The 96-h LC 50 values were 0.477 mg/L for pendimethalin and 2.634 mg/L for fenitrothion.Joint exposure produced enhanced toxicity,with 96-h LC 50 values of 0.204 mg/L(pendimethalin equivalent)and 1.139 mg/L(fenitrothion equivalent).Regression analysis showed a significant positive correlation(p<0.05)between pesticide concentration and mortality,while toxicity indices confirmed synergistic interactions.These findings underscore the ecological risks posed by pesticide mixtures and highlight the importance of regulating pesticide use to safeguard aquatic organisms and maintain environmental sustainability.
基金Supported by the Central Public-interest Scientific Institution Basal Research Fund,CAFS(2025XT0902)the earmarked fund for China Agriculture Research System(CARS-46).
文摘This study attempted to assess the lethal concentration(96-h LC_(50))effects of imidacloprid(neonicotinoid pesticide),thiamethoxam(neonicotinoid pesticide),and their combination on juvenile Zebrafish(Danio rerio).Each set of trials contained a control(de-chlorinated tap water),and the experiments were repeated three times.The fish(n=10)were randomly measured with an average length of(3.4±0.34)cm and weight of(1±0.1)g.The temperature was kept at 24℃.Experiments 1 and 2 were designed to investigate at the acute toxicity of imidacloprid and thiamethoxam on juvenile zebrafish(Danio rerio)respectively,whereas experiment 3 was aimed at the combined toxicity of IMI and THM on zebrafish.The tests followed the same study design,and each experiment used seven different logarithmic concentrations of imidacloprid insecticides(310.00,317.08,324.33,331.74,339.32,347.07,355.00 mg/L)and thiamethoxam(175.00,185.52,200.93,215.30,230.70,247.20,264.88 mg/L).The results show that THM is more toxic than IMI,with LC_(50)values of 190.34 mg/L for THM and 310.92 mg/L for IMI.Both individual toxicities showed a substantial positive connection(P<0.05)with confidence limits of 321.50-300.68 mg/L for IMI and 199.91-181.21 mg/L for THM.The joint toxicity test was carried out using the 96-h LC_(50)values of imidacloprid and thiamethoxam obtained in the individual acute toxicity trials at a 1:1 ratio.The Additive Index(AI)demonstrated that imidacloprid and thiamethoxam acted synergistically on D.rerio.As a matter of fact,more research is needed to better understand the impact of IMI and THM on other aquatic organisms and also create strategies to mitigate its harmful effects on aquatic life.
基金This work was supported by the Focused Research Effort on Chemicals in the Working Environment(FFIKA)from the Danish Government.
文摘Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration technique,where the test substance is suspended in a liquid vehicle and deposited into the lung via the trachea.Instillation requires minimal test material,delivers an exact dose deep into the lung,and is less labor-intensive than inhalation exposures.However,one shortcoming is that the pro-cedure may induce short-term inflammation.To minimize this,we tested different modifications of the technique to identify the potential for refinement.Methods:First,we tested whether previous findings of increased inflammation could be confirmed.Next,we tested whether instillation with a disposable 1 mL syringe with ball-tipped steel-needle(Disposable-syringe/steel-needle)induced less inflammation than the use of our standard set-up,a 250μL reusable glass syringe with a disposable plastic catheter(Glass-syringe/plastic-catheter).Finally,we tested if access to pelleted and liquid feed prior to instillation affected inflammation.We evaluated inflammation by neutrophil numbers in bronchoalveolar fluid 24 h post-exposure.Results:Vehicle-instilled mice showed a small increase in neutrophil numbers com-pared to untreated mice.Neutrophil numbers were slightly elevated in the groups in-stilled with Disposable-syringe/steel-needle;an interaction with feed type indicated that the increase in neutrophils was more pronounced in combination with feed pel-lets compared to liquid feed.We found no difference between the feed types when using the Glass-syringe/plastic-catheter combination.Conclusion:The Glass-syringe/plastic-catheter combination induced the least exposure-related inflammation,confirming this as a preferred instillation procedure.
文摘To evaluate the subchronic and chronic toxicity of Fuyanxiao capsules,Sprague-Dawley(SD)rats were used in toxicity studies.In the subchronic toxicity study,50 female rats were randomly divided into a high-dose group(5.4g/kg/day)and a control group,with 15 rats in each,and medium(2.7g/kg/day)and low(1.35g/kg/day)dose groups,with 10 rats in each.The test substance was administered orally(mixed with feed,twice daily)for 90 consecutive days.In the chronic toxicity study,40 female rats were randomly divided into high,medium,and low dose groups and a control group,with 10 rats in each.The test substance was administered orally in the same manner for 180 consecutive days.Clinical signs,body weight,and food consumption were observed and recorded daily.At the end of the terminal phase(the first 10 rats from each group,1 day after the last dose)and the recovery phase(the last 5 rats from the control group and the high-dose group,observed for an additional 28 days after the last dose),blood and urine samples,as well as organs,were collected.Organ coefficients were calculated,and various hematological and urinary indicators were detected,followed by pathological analysis.The results showed that there were no significant differences in body weight,food consumption,or organ coefficients between any of the dose groups and the control group in both subchronic and chronic toxicity studies(P>0.05).Histopathological examination revealed no lesions,suggesting no tissue or organ damage in any of the dose groups.The rats exhibited good mental status,and hematological and urinary physiological indicators were within normal ranges,indicating stable liver and kidney function,hematopoietic system of the bone marrow,and internal environment in all dose groups.Therefore,Fuyanxiao capsule has no obvious subchronic or chronic toxicity in SD rats,and it is safe and reliable to use at reasonable dosage in clinical practice.
