Objective: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety,Methods: Acute toxicity was determined by oral administration of a single dose of 18 100 mg/kg forsythin in NIH mic...Objective: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety,Methods: Acute toxicity was determined by oral administration of a single dose of 18 100 mg/kg forsythin in NIH mice,Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0,540,1 620,and 6 480 mg/kg in SD rats.Results: In the acute toxicity study,mortality was not observed after 14 days,In addition,clinically relevant adverse effects,or variations in body weight or food consumption were not observed,Similarly,after 30 days in the sub-chronic toxicity study,no mortality or significant toxicological effects such as decreased food consumption,body weight,biochemical parameters and vital organs etc,were noticed,Conclusion: The results revealed that the forsythin from Forsythia suspensa leaves has low or no toxicity via oral administration,and therefore is suitable for further development and applications.展开更多
Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establi...Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establish the toxicity profile of the alkaloid extract(TA)of A.scholaris leaves in non-rodents.After oral administration of a single dose(4 g/kg.bw),a num-ber of transient symptoms,such as unsteady gait,drooling,emesis,and reddening of peri-oral mucosa,were observed,but no treatment-related mortality.A sub-chronic toxicity study with a range of doses of TA(20,60 and 120 mg/kg.bw)was conducted for a 13-week treatment period,followed by 4-week recovery observation.Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group,no clinical changes were observed in TA-treated animals.Data from electrocardiography,bone marrow,urine,fecal,hematology and clinical chemistry analyses were comparable between TA-treated and control animals.No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups.Accordingly,the non-observed-adverse-effect-level(NOAEL)of TA was established as 120 mg/kg.bw.Our results add further knowledge to the safety database for indole alkaloid extracts from A.scholaris with potential utility as novel drug candidates.展开更多
A total of 40 Wistar rats, weighing 130-140 g, were allocated randomly into four groups. They were orally administrated with 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and...A total of 40 Wistar rats, weighing 130-140 g, were allocated randomly into four groups. They were orally administrated with 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg aluminum chloride （AlCl3） per kilogram body weight in drinking water for 120 days. Kidney coefficient and aluminum （Al） concentrations in blood and kidney were determined, and renal autopsy and histological changes were observed. The results showed that kidney coefficient in all Al-treated groups were obviously lower than that in GC （P〈0.01） and there was a dose-effect relationship. The kidneys were solid, lusterless and pale brown with white necrosis point on surface. Under electron microscope, renal cortex became thin, the renal tubule was narrowed and the epithelium dissolved; the renal glomerulus became atrophied and the glomerular became vasodilator. The Al concentrations in blood and kidney were higher in all Al-treated rats than those in GC （P〈0.01）, and there was a dose-effect relationship. The results indicated that sub-chronic Al exposure could lead to Al accumulation in kidney, restrain the development of kidney and cause the pathologic damage in rats.展开更多
[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17...[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17 g were randomly divided into four groups （forty mice per group）. Mice were injected to 1, 8 - cineole with doses of 192.45,64. 15 and 21.38 mg/kg body weight （ test groups） and the water solution of tween-80 with a volume fraction of 0.5% （ control group） respectively. Each mouse was administered orally at the dose of 0.2 mL per 10 g body weight once a day consecutively for 90 d. The body weight, routine blood indexes and serum biochemical indexes of mice were determined on the 30^th d, 60^th d, 90^th d and the 30^th d after stopping the administration of 1,8-cineole. [ Result] The effects of 1, 8-cineole on the body weight, routine blood indexes and serum biochemical indexes of mice with the doses of 64.15 and 21.38 mg/kg body weight had no statistically significant difference compared with the control group （P 〉0.05 ）. 1, 8-cineole with the dose of 192.45 mg/kg body weight exhibited different influences on routine blood indexes and serum biochemical indexes of mice after the oral administration of 1,8-cineole for 60 d and 90 d, and statistically significant differences in many blood biochemical indexes were observed （P 〈 0.05 ）. However, the differences in routine blood indexes and serum biochemical indexes were not statistically significant between the test groups and the control group at the 30＇h d after stopping the administration of 1, 8-cineole （ P 〉 0.05）. [Condusion] 1,8-cineole had sub-chronic oral toxicity to mice. The no observed adverse effect level （NOAEL） of 1,8-cineolc was 64.15 mg/kg body weight and the lowest observed adverse effect level （LOAEL） of 1,8-cineole was 192.45 mg/kg body weight. Effects of 1, 8-cineole on blood biochemical indexes of mice were in short term and reversible.展开更多
To investigate the effects of aluminurn （Al） exposure on renal structure of rats, 60 Wistar rats were randomly divided into four treatment groups and were orally exposed to 0 （control group, GC）, 64.18 （low-dose ...To investigate the effects of aluminurn （Al） exposure on renal structure of rats, 60 Wistar rats were randomly divided into four treatment groups and were orally exposed to 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg· kg^-1 BW AlCl3 in drinking water for 120 days. The body weight of different rats was recorded, the kidney pathologic structure and the ultrastructure were observed. The results showed that the body weight of different rats was markedly lower in Al-treated rats than those in GC （P〈0.05; P〈0.01）. After masson staining, the collagen was deposited in the renal interstitium and aggravated with Al dose increases in Al-treated rats. Under electron microscope, the infolding of the plasma membrane was slight swollen, the mitochondrion was abundant with different sizes, the mitochondrion cristae was fused, the microvillus was swollen and fused in GH. Our findings indicated that sub-chronic A1 exposure slowed the weight of rats and caused the kidney pathologic damage in rats.展开更多
[ Objective] To observe sub-chronic toxicity of Tephrosia canadida DC. in mice and thus to evaluate their safety to be used as protein feed resources. [ Methed]Sixty-four 6-week-old healthy Kunming mice weighing about...[ Objective] To observe sub-chronic toxicity of Tephrosia canadida DC. in mice and thus to evaluate their safety to be used as protein feed resources. [ Methed]Sixty-four 6-week-old healthy Kunming mice weighing about 25 g were randomly divided into four groups （ n = 16）, half male and half female. Mass ratios of basic diet to leaf meal of Tephrosia canadida DC. in group A, group B, group C and group D were 10：0, 4：1, 3：2 and 2：3, respectively. After 35-d feeding, the effects of Tephrosia canadida DC. on growth, blood and organs of mice were observed. [ Resultl Dudng the trial, all mice had normal activities, and no death and no abnormal blood index were observed. All organs of the mice in the experimental groups had no visible pathological lesion, and organ indexes had no significant difference between the experimental groups and the control group. Except that slightly abnormal histological changes appeared in liver and kidney of the mice in the group C and D, no histological change was ob- served in other organs of the experimental mice. [ Conclusion] Tephrosia canadida DC. have no adverse effects on mice, which provides a refer- ence for research about their safety in feed of other animals.展开更多
Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of t...Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of the stem bark of Bridelia micrantha using column chromatographic techniques. The fraction F6 was the most active when tested for antibacterial activity. Thus, toxicity of this fraction was investigated for further use. The present study evaluated the acute and sub-chronic toxicity of the crude methanolic bark extract of Bridelia micrantha and its fraction. The acute toxicity was carried out according to the experimental protocol of Organization for Economic Co-operation and Development (OECD). The plant extract or the fraction F<sub>6</sub> was administered orally to female mice at a single dose of 2000 mg/kg and the animals were observed for any behavioral changes or mortality for 14 days. In the sub-chronic toxicity study, the extract and fraction were administered orally at 200, 400 and 800 mg/kg bw/day for 28 days to healthy Wistar rats. The general behavior and body weight of the rats were recorded daily. At the end of the experimental period, hematological and biochemical analyses, changes in vital organ weight (liver, lung, heart, spleen and kidney), and histopathological examination of the liver and kidney were performed. No mortality or adverse effects were noted at the 2000 mg/kg dose during the oral acute toxicity test. In the sub-chronic study, the crude methanolic bark extract of Bridelia micrantha and the fraction F<sub>6</sub> induced no mortality or treatment-related adverse effects on body weight, general behavior, relative organ weights, hematological and biochemical parameters. Histopathological examination of the liver and kidney showed normal architecture suggesting no morphological alterations. In conclusion, the oral administration of the crude methanolic bark extract of Bridelia micrantha and the fraction F<sub>6</sub> for 28 days at a dosage of up to 800 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD<sub>50</sub>) of the crude methanolic bark extract of Bridelia micrantha and the fraction F<sub>6</sub> was estimated to be more than 2000 mg/kg.展开更多
Objective To explore the possible long‐term health effects of the defoamer used in seawater desalination by sub‐chronic toxicity testing. Methods Blood analysis, internal organ assessment, and histopathological exam...Objective To explore the possible long‐term health effects of the defoamer used in seawater desalination by sub‐chronic toxicity testing. Methods Blood analysis, internal organ assessment, and histopathological examination were carried out in rats exposed to low, medium, and high(0.5, 1.0, and 2.0 g/kg BW, respectively) doses of defoamer for 90 days through oral administration. Results The high dose group showed decreased blood alanine aminotransferase and aspartate aminotransferase(P < 0.05). All doses resulted in a significant increase in albumin and decrease in globulin(P < 0.05). The direct bilirubin and indirect bilirubin were decreased in the medium and high dose groups(P < 0.05). All dose groups showed significant induction of alkaline phosphatase(P < 0.05). Pathological examination revealed a case of liver mononuclear cell infiltration in the medium dose group and three cases of liver congestion, steatosis of hepatic cells around the central vein, and punctate necrosis with multiple focal mononuclear cell infiltration in male rats administered the high dose. The No Observed Adverse Effect Level was 0.5 g/kg BW in rats, with albumin and total bilirubin as health effect indices. Conclusion Long‐term defoamer exposure may cause liver injury but has no significant impact on renal function in rats. The effect on blood cells in female rats was more prominent than that in male rats.展开更多
Objective： To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine（TET） in female BALB/c mice. Methods： The median lethal dose（LD_（50）） of intravenously administered TET was ca...Objective： To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine（TET） in female BALB/c mice. Methods： The median lethal dose（LD_（50）） of intravenously administered TET was calculated in mice using Dixon＇s up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET（30, 90 and 150 mg/kg） each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. Result： LD_（50） was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically significant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET（P〉0.05）. In the sub-acute toxicity study, no significant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group（P〉0.05）, however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. Conclusions： The overall findings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.展开更多
Coenzyme Q_(10)(CoQ_(10))is a crucial endogenous lipophilic antioxidant,and encapsulation is often used to improve its solubility and stability.However,information about the bioavailability and safety assessment of co...Coenzyme Q_(10)(CoQ_(10))is a crucial endogenous lipophilic antioxidant,and encapsulation is often used to improve its solubility and stability.However,information about the bioavailability and safety assessment of constructed formulations is limited.In this study,in vivo pharmacokinetics profile and sub-chronic toxicity of CoQ_(10) loaded whey protein concentrate(WPC)and polymerized whey protein concentrate(PWPC)nanoparticles were evaluated.Pharmacokinetics data showed that CoQ_(10) concentrations in the plasma of rats fed with nanoparticles were higher than that of the free counterpart.CoQ_(10) concentration reached its maximum level after 12 h when orally administered with WPC and PWPC based encapsulation,which was delayed compared with free CoQ_(10)(8 h).Sub-chronic toxicity evaluation for PWPC-CoQ_(10) was conducted with 28-day feeding test.Results indicated that no adverse toxicological reactions in term of physical examination,body weight,food intake,hematology,serum chemistry,organ weight or histopathology excepted for blood potassium were observed after oral administration of feed with incorporated PWPC-CoQ_(10) nanoparticles.The maximum concentration of nanoparticle powder in diet of no adverse effect on the male and female rats was up to 2%(w/w).Results denoted a potential application of whey protein as a safe natural polymer to fabricate delivery systems to enhance bioavailability of nutritional supplements like CoQ_(10).展开更多
Background:Phyto-medicine represents a vast pool of novel drug development,but understanding their safety requires elaborate,multifaceted approaches,including toxicity studies.Objective:This study investigated the eff...Background:Phyto-medicine represents a vast pool of novel drug development,but understanding their safety requires elaborate,multifaceted approaches,including toxicity studies.Objective:This study investigated the effects of 90 days of oral administration of Datura stramonium(DSE)leaf extract in Rats.Methods:In the oral acute toxicity study,mice were treated with a single oral gavage of DSE at 500,1000,and 2000 mg·kg^(-1)/d,po and observed for signs of acute toxicity for 14 days.In the sub-chronic study,rats were randomized into four Groups(A-D).Group A received distilled water(10 mL·kg^(-1),po)while groups B-D received DSE(10,50 and 250 mg·kg^(-1)/d,po,respectively)orally for 90 days uninterrupted.Animals were weighed weekly,with food and water measured daily and relevant parameters assayed at the end of the 90days administration.Results:In acute toxicity studies,oral administration of up to 2 g·kg^(-1)/d,po of DSE did not elicit any semblance of toxicity or mortality within 24 h to 14 days.In the 90days studies,DSE(250 mg·kg^(-1)/d,po)decreased the body weight,brain weight,and food intake in female rats.DSE(10-250 mg·kg^(-1)/d,po)increased the red blood cell(RBC),packed cell volume(PCV)and hemoglobin(Hb)in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the triglycerides(TG),cholesterol and low-density lipoprotein(LDL);and decreased HDL in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the white blood cells(WBC)and platelets in female rats.DSE(10-250 mg·kg^(-1)/d,po)decreased the alkaline phosphatase(ALP)and alanine transaminase(ALT)in both studies.Serum urea level was decreased in both sexes.DSE(250 mg·kg^(-1)/d,po)decreased male rats’serum sodium ion levels.Liver,brain,testes and kidney showed severe lesions at 250 mg·kg^(-1)/d,po of the extract.Conclusion:D.stramonium is safe on acute exposure and relatively safe on sub-chronic oral administration.How-ever,prolonged use,especially at high doses,could cause Liver,brain and kidney toxicities;and abnormal lipid metabolism.展开更多
基金supported by the Basic Science Research Program of Guangdong Province Science and Technology Plan Projects Fund[grant numbers:2016A010119136]the High-level Leading Talent Introduction Program of GDAS[grant numbers:2016GDASRC-0104]
文摘Objective: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety,Methods: Acute toxicity was determined by oral administration of a single dose of 18 100 mg/kg forsythin in NIH mice,Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0,540,1 620,and 6 480 mg/kg in SD rats.Results: In the acute toxicity study,mortality was not observed after 14 days,In addition,clinically relevant adverse effects,or variations in body weight or food consumption were not observed,Similarly,after 30 days in the sub-chronic toxicity study,no mortality or significant toxicological effects such as decreased food consumption,body weight,biochemical parameters and vital organs etc,were noticed,Conclusion: The results revealed that the forsythin from Forsythia suspensa leaves has low or no toxicity via oral administration,and therefore is suitable for further development and applications.
基金The authors are grateful to Yunnan Major Science and Technology Project(2019ZF003,2019FY003004)the National Key Research and Development Program of China(2017YFC1704007)the general program of applied basic research of Yunnan province(2019FB116)for partial financial support.
文摘Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establish the toxicity profile of the alkaloid extract(TA)of A.scholaris leaves in non-rodents.After oral administration of a single dose(4 g/kg.bw),a num-ber of transient symptoms,such as unsteady gait,drooling,emesis,and reddening of peri-oral mucosa,were observed,but no treatment-related mortality.A sub-chronic toxicity study with a range of doses of TA(20,60 and 120 mg/kg.bw)was conducted for a 13-week treatment period,followed by 4-week recovery observation.Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group,no clinical changes were observed in TA-treated animals.Data from electrocardiography,bone marrow,urine,fecal,hematology and clinical chemistry analyses were comparable between TA-treated and control animals.No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups.Accordingly,the non-observed-adverse-effect-level(NOAEL)of TA was established as 120 mg/kg.bw.Our results add further knowledge to the safety database for indole alkaloid extracts from A.scholaris with potential utility as novel drug candidates.
基金Supported by the Postgraduate Innovative Scientific Research Foundation Program of Helongjiang Province (YJSCX2012-026HLJ)
文摘A total of 40 Wistar rats, weighing 130-140 g, were allocated randomly into four groups. They were orally administrated with 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg aluminum chloride （AlCl3） per kilogram body weight in drinking water for 120 days. Kidney coefficient and aluminum （Al） concentrations in blood and kidney were determined, and renal autopsy and histological changes were observed. The results showed that kidney coefficient in all Al-treated groups were obviously lower than that in GC （P〈0.01） and there was a dose-effect relationship. The kidneys were solid, lusterless and pale brown with white necrosis point on surface. Under electron microscope, renal cortex became thin, the renal tubule was narrowed and the epithelium dissolved; the renal glomerulus became atrophied and the glomerular became vasodilator. The Al concentrations in blood and kidney were higher in all Al-treated rats than those in GC （P〈0.01）, and there was a dose-effect relationship. The results indicated that sub-chronic Al exposure could lead to Al accumulation in kidney, restrain the development of kidney and cause the pathologic damage in rats.
基金Supported by the Incubation Program for Science and Technology Innovative Research Team in Sichuan Province of China(2011-JTD0035)Program of Department of Education in Sichuan Province of China(10ZB050)the Program of Department of Education in Sichuan Province of China(11ZZ022)
文摘[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17 g were randomly divided into four groups （forty mice per group）. Mice were injected to 1, 8 - cineole with doses of 192.45,64. 15 and 21.38 mg/kg body weight （ test groups） and the water solution of tween-80 with a volume fraction of 0.5% （ control group） respectively. Each mouse was administered orally at the dose of 0.2 mL per 10 g body weight once a day consecutively for 90 d. The body weight, routine blood indexes and serum biochemical indexes of mice were determined on the 30^th d, 60^th d, 90^th d and the 30^th d after stopping the administration of 1,8-cineole. [ Result] The effects of 1, 8-cineole on the body weight, routine blood indexes and serum biochemical indexes of mice with the doses of 64.15 and 21.38 mg/kg body weight had no statistically significant difference compared with the control group （P 〉0.05 ）. 1, 8-cineole with the dose of 192.45 mg/kg body weight exhibited different influences on routine blood indexes and serum biochemical indexes of mice after the oral administration of 1,8-cineole for 60 d and 90 d, and statistically significant differences in many blood biochemical indexes were observed （P 〈 0.05 ）. However, the differences in routine blood indexes and serum biochemical indexes were not statistically significant between the test groups and the control group at the 30＇h d after stopping the administration of 1, 8-cineole （ P 〉 0.05）. [Condusion] 1,8-cineole had sub-chronic oral toxicity to mice. The no observed adverse effect level （NOAEL） of 1,8-cineolc was 64.15 mg/kg body weight and the lowest observed adverse effect level （LOAEL） of 1,8-cineole was 192.45 mg/kg body weight. Effects of 1, 8-cineole on blood biochemical indexes of mice were in short term and reversible.
基金Supported by the Science and Technology Program of Heilongjiang Educational Bureau(12541025)the Natural Science Foundation of Heilongjiang Province(C201425)
文摘To investigate the effects of aluminurn （Al） exposure on renal structure of rats, 60 Wistar rats were randomly divided into four treatment groups and were orally exposed to 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg· kg^-1 BW AlCl3 in drinking water for 120 days. The body weight of different rats was recorded, the kidney pathologic structure and the ultrastructure were observed. The results showed that the body weight of different rats was markedly lower in Al-treated rats than those in GC （P〈0.05; P〈0.01）. After masson staining, the collagen was deposited in the renal interstitium and aggravated with Al dose increases in Al-treated rats. Under electron microscope, the infolding of the plasma membrane was slight swollen, the mitochondrion was abundant with different sizes, the mitochondrion cristae was fused, the microvillus was swollen and fused in GH. Our findings indicated that sub-chronic A1 exposure slowed the weight of rats and caused the kidney pathologic damage in rats.
文摘[ Objective] To observe sub-chronic toxicity of Tephrosia canadida DC. in mice and thus to evaluate their safety to be used as protein feed resources. [ Methed]Sixty-four 6-week-old healthy Kunming mice weighing about 25 g were randomly divided into four groups （ n = 16）, half male and half female. Mass ratios of basic diet to leaf meal of Tephrosia canadida DC. in group A, group B, group C and group D were 10：0, 4：1, 3：2 and 2：3, respectively. After 35-d feeding, the effects of Tephrosia canadida DC. on growth, blood and organs of mice were observed. [ Resultl Dudng the trial, all mice had normal activities, and no death and no abnormal blood index were observed. All organs of the mice in the experimental groups had no visible pathological lesion, and organ indexes had no significant difference between the experimental groups and the control group. Except that slightly abnormal histological changes appeared in liver and kidney of the mice in the group C and D, no histological change was ob- served in other organs of the experimental mice. [ Conclusion] Tephrosia canadida DC. have no adverse effects on mice, which provides a refer- ence for research about their safety in feed of other animals.
文摘Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of the stem bark of Bridelia micrantha using column chromatographic techniques. The fraction F6 was the most active when tested for antibacterial activity. Thus, toxicity of this fraction was investigated for further use. The present study evaluated the acute and sub-chronic toxicity of the crude methanolic bark extract of Bridelia micrantha and its fraction. The acute toxicity was carried out according to the experimental protocol of Organization for Economic Co-operation and Development (OECD). The plant extract or the fraction F<sub>6</sub> was administered orally to female mice at a single dose of 2000 mg/kg and the animals were observed for any behavioral changes or mortality for 14 days. In the sub-chronic toxicity study, the extract and fraction were administered orally at 200, 400 and 800 mg/kg bw/day for 28 days to healthy Wistar rats. The general behavior and body weight of the rats were recorded daily. At the end of the experimental period, hematological and biochemical analyses, changes in vital organ weight (liver, lung, heart, spleen and kidney), and histopathological examination of the liver and kidney were performed. No mortality or adverse effects were noted at the 2000 mg/kg dose during the oral acute toxicity test. In the sub-chronic study, the crude methanolic bark extract of Bridelia micrantha and the fraction F<sub>6</sub> induced no mortality or treatment-related adverse effects on body weight, general behavior, relative organ weights, hematological and biochemical parameters. Histopathological examination of the liver and kidney showed normal architecture suggesting no morphological alterations. In conclusion, the oral administration of the crude methanolic bark extract of Bridelia micrantha and the fraction F<sub>6</sub> for 28 days at a dosage of up to 800 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD<sub>50</sub>) of the crude methanolic bark extract of Bridelia micrantha and the fraction F<sub>6</sub> was estimated to be more than 2000 mg/kg.
基金supported by the Scientific Research Project on Marine Public Welfare Industry [No.201505021] of National Oceanic Administration’s in China
文摘Objective To explore the possible long‐term health effects of the defoamer used in seawater desalination by sub‐chronic toxicity testing. Methods Blood analysis, internal organ assessment, and histopathological examination were carried out in rats exposed to low, medium, and high(0.5, 1.0, and 2.0 g/kg BW, respectively) doses of defoamer for 90 days through oral administration. Results The high dose group showed decreased blood alanine aminotransferase and aspartate aminotransferase(P < 0.05). All doses resulted in a significant increase in albumin and decrease in globulin(P < 0.05). The direct bilirubin and indirect bilirubin were decreased in the medium and high dose groups(P < 0.05). All dose groups showed significant induction of alkaline phosphatase(P < 0.05). Pathological examination revealed a case of liver mononuclear cell infiltration in the medium dose group and three cases of liver congestion, steatosis of hepatic cells around the central vein, and punctate necrosis with multiple focal mononuclear cell infiltration in male rats administered the high dose. The No Observed Adverse Effect Level was 0.5 g/kg BW in rats, with albumin and total bilirubin as health effect indices. Conclusion Long‐term defoamer exposure may cause liver injury but has no significant impact on renal function in rats. The effect on blood cells in female rats was more prominent than that in male rats.
基金Supported by the National Natural Science Foundation of China(No.81171542 and No.81471995)
文摘Objective： To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine（TET） in female BALB/c mice. Methods： The median lethal dose（LD_（50）） of intravenously administered TET was calculated in mice using Dixon＇s up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET（30, 90 and 150 mg/kg） each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. Result： LD_（50） was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically significant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET（P〉0.05）. In the sub-acute toxicity study, no significant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group（P〉0.05）, however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. Conclusions： The overall findings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.
文摘Coenzyme Q_(10)(CoQ_(10))is a crucial endogenous lipophilic antioxidant,and encapsulation is often used to improve its solubility and stability.However,information about the bioavailability and safety assessment of constructed formulations is limited.In this study,in vivo pharmacokinetics profile and sub-chronic toxicity of CoQ_(10) loaded whey protein concentrate(WPC)and polymerized whey protein concentrate(PWPC)nanoparticles were evaluated.Pharmacokinetics data showed that CoQ_(10) concentrations in the plasma of rats fed with nanoparticles were higher than that of the free counterpart.CoQ_(10) concentration reached its maximum level after 12 h when orally administered with WPC and PWPC based encapsulation,which was delayed compared with free CoQ_(10)(8 h).Sub-chronic toxicity evaluation for PWPC-CoQ_(10) was conducted with 28-day feeding test.Results indicated that no adverse toxicological reactions in term of physical examination,body weight,food intake,hematology,serum chemistry,organ weight or histopathology excepted for blood potassium were observed after oral administration of feed with incorporated PWPC-CoQ_(10) nanoparticles.The maximum concentration of nanoparticle powder in diet of no adverse effect on the male and female rats was up to 2%(w/w).Results denoted a potential application of whey protein as a safe natural polymer to fabricate delivery systems to enhance bioavailability of nutritional supplements like CoQ_(10).
文摘Background:Phyto-medicine represents a vast pool of novel drug development,but understanding their safety requires elaborate,multifaceted approaches,including toxicity studies.Objective:This study investigated the effects of 90 days of oral administration of Datura stramonium(DSE)leaf extract in Rats.Methods:In the oral acute toxicity study,mice were treated with a single oral gavage of DSE at 500,1000,and 2000 mg·kg^(-1)/d,po and observed for signs of acute toxicity for 14 days.In the sub-chronic study,rats were randomized into four Groups(A-D).Group A received distilled water(10 mL·kg^(-1),po)while groups B-D received DSE(10,50 and 250 mg·kg^(-1)/d,po,respectively)orally for 90 days uninterrupted.Animals were weighed weekly,with food and water measured daily and relevant parameters assayed at the end of the 90days administration.Results:In acute toxicity studies,oral administration of up to 2 g·kg^(-1)/d,po of DSE did not elicit any semblance of toxicity or mortality within 24 h to 14 days.In the 90days studies,DSE(250 mg·kg^(-1)/d,po)decreased the body weight,brain weight,and food intake in female rats.DSE(10-250 mg·kg^(-1)/d,po)increased the red blood cell(RBC),packed cell volume(PCV)and hemoglobin(Hb)in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the triglycerides(TG),cholesterol and low-density lipoprotein(LDL);and decreased HDL in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the white blood cells(WBC)and platelets in female rats.DSE(10-250 mg·kg^(-1)/d,po)decreased the alkaline phosphatase(ALP)and alanine transaminase(ALT)in both studies.Serum urea level was decreased in both sexes.DSE(250 mg·kg^(-1)/d,po)decreased male rats’serum sodium ion levels.Liver,brain,testes and kidney showed severe lesions at 250 mg·kg^(-1)/d,po of the extract.Conclusion:D.stramonium is safe on acute exposure and relatively safe on sub-chronic oral administration.How-ever,prolonged use,especially at high doses,could cause Liver,brain and kidney toxicities;and abnormal lipid metabolism.
