AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the ...AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver damage,which was confirmed by liver histology.In addition,HL combined with I/R also caused significantly increased hepatocyte apoptosis,as evidenced by increased TUNEL-positive cells(6.20 ± 0.29 vs 1.5 ± 0.22,4.47 ± 0.45 or 1.97 ± 0.47,P < 0.01),elevated expression of caspase-3 and lower expression of bcl-2.Furthermore,when compared to HL or I/R alone,HL plus I/R enhanced serum TNF-,IL-1,liver mitochondrial MDA and Ca 2+ levels,suppressed SOD and GSH-Px in liver mitochondria,and markedly up-regulated the activity(11.76 ± 2.36 vs 4.77 ± 2.31 or 3.11 ± 1.35,P < 0.01) and expression(3.24 ± 0.38 vs 1.98 ± 0.88 or 1.72 ± 0.58,P < 0.01) of CYP2E1 in liver.CONCLUSION:The coexistence of HL and acute cerebral I/R induces severe liver damage,suggesting that cerebral ischemic stroke would exaggerate the damage of liver caused by HL.This effect is possibly due to en-hanced CYP2E1 induction which further promotes oxidative damage,inflammation and hepatocyte apoptosis.展开更多
AIM: To evaluate the effects of extrahepatic collaterals to the liver on liver damage and patient outcome after embolotherapy for the ruptured hepatic artery pseudoa- neurysm following hepatobiliary pancreatic surgery...AIM: To evaluate the effects of extrahepatic collaterals to the liver on liver damage and patient outcome after embolotherapy for the ruptured hepatic artery pseudoa- neurysm following hepatobiliary pancreatic surgery. METHODS: We reviewed 9 patients who underwent transcatheter arterial embolization (TAE) for the ruptured hepatic artery pseudoaneurysm following major hepato- biliary pancreatic surgery between June 1992 and April 2006. We paid special attention to the extrahepatic arte- rial collaterals to the liver which may affect post-TAE liver damage and patient outcome. RESULTS: The underlying diseases were all malignan- cies, and the surgical procedures included hepatopancre- atoduodenectomy in 2 patients, hepatic resection with removal of the bile duct in 5, and pancreaticoduodenec- tomy in 2. A total of 11 pseudoaneurysm developed: 4 in the common hepatic artery, 4 in the proper hepatic artery, and 3 in the right hepatic artery. Successful he- mostasis was accomplished with the initial TAE in all patients, except for 1. Extrahepatic arterial pathways to the liver, including the right inferior phrenic artery, the jejunal branches, and the aberrant left hepatic artery, were identified in 8 of the 9 patients after the completion of TAE. The development of collaterals depended on the extent of liver mobilization during the hepatic resection, the postoperative period, the presence or absence of an aberrant left hepatic artery, and the concomitant arte- rial stenosis adjacent to the pseudoaneurysm. The liver tolerated TAE without significant consequences when at least one of the collaterals from the inferior phrenic ar-tery or the aberrant left hepatic artery was present. One patient, however, with no extrahepatic collaterals died of liver failure due to total liver necrosis 9 d after TAE. CONCLUSION: When TAE is performed on ruptured hepatic artery pseudoaneurysm, reduced collateral path- ways to the liver created by the primary surgical proce- dure and a short postoperative interval may lead to an unfavorable outcome.展开更多
This study explored the therapeutic effects of Auricularia auricula melanin(AAM)on alcoholic liver damage in vitro and in vivo.Human normal liver L02 cells were pre-treated with ethanol and then treated with AAM to ex...This study explored the therapeutic effects of Auricularia auricula melanin(AAM)on alcoholic liver damage in vitro and in vivo.Human normal liver L02 cells were pre-treated with ethanol and then treated with AAM to explore the therapeutic effect of AAM on ethanol-induced hepatocyte injury.The results show that AAM signifi cantly elevated the cell viability,ameliorated the cell morphology,reduced the ROS and increased the GSH/GSSG of ethanol-pretreated L02 cells.Then,mice were administered with ethanol to induce acute alcoholic liver damage,and administered with AAM to further study the therapeutic effect of AAM on alcoholic liver damage in mice.As a result,AAM reduced the levels of ALT,AST,TG,and MDA,increased the levels of ADH,SOD,and CAT in liver damage mice.The therapeutic effect of AAM may be related to inhibition of CYP2E1 expression and activation of Nrf2 and its downstream antioxidase.The research enriched the bioactivity of AAM and provided some ideas for the development of melanin-related health foods.展开更多
AIM： To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan （GB34） on CCl4-induced chronic liver damage in rats. METHODS： Rats were injected intraperitoneally with CCh （1 mL/kg） and tre...AIM： To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan （GB34） on CCl4-induced chronic liver damage in rats. METHODS： Rats were injected intraperitoneally with CCh （1 mL/kg） and treated with manual acupuncture using reinforcing manipulation techniques at left GB34 （Yanglingquan） 3 times a week for 10 wk. A nonacupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index, biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted. RESULTS： Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes. CONCLUSION： Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCh-intoxicated rats.展开更多
AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS...AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS After staphylococcal enterotoxin B(SEB ) mixed with D--galactosamine (D-GaiN )were injected intraperitoneally into Balb/c miceand those previously treated with cyclosporin A,blood samples were collected and livers wereisolated at 2, 6, 12 and 24 h. Patterns othepatocellular death were studiedmorphologically and biochemically, circulatingcytokines (TNF-a, IFN--y ) and mice mortalitywithin 24h was assessed.RESU’LTS The SEB could induce the typicalapoptotic changes of hepatocytes, the D-GaiNcould induce hepatocytes apoptosis anddegeneration at the same time, and the micehaving received the SEB + D-GaiN injectionsdeveloped apoptosis at 2 and 6 h, but after 12 hhepatocytes were characterized by severein jury, whereas all the examinations in thecyclosporin A treated mice were normal.CONCLUSION Hepatic cell apoptosis might berelated to necrosis, and massive hepatocyteapoptosis is likely the initiating step of acutehepatic necrosis in mice. The effects induced bySEB and D--GaiN on hepatocytes might bemediated by T cells, and could be prevented bycyclosporin A.展开更多
The aim of this study is to investigate the feasibility of Maillard reaction products of Haematococcus pluvialis protein and galactose(HPP-GAL)for improving the bioactivities of curcumin(CUR)for alleviating alcoholic ...The aim of this study is to investigate the feasibility of Maillard reaction products of Haematococcus pluvialis protein and galactose(HPP-GAL)for improving the bioactivities of curcumin(CUR)for alleviating alcoholic liver damage.CUR was embedded into HPP-GAL nanoparticles by the self-assembly of hydrogen bonding and hydrophobic interaction with the particle size around 200 nm.HPP-GAL enhanced the encapsulation efficiency and loading amount of CUR with the value of(89.21±0.33)%and(0.500±0.004)%,respectively.The stabilities of CUR under strong acid,salt ion stability and ultraviolet irradiation conditions were improved by the encapsulation.HPP-GAL-CUR nanoparticles exhibited excellent concentration-dependent in vitro antioxidant activities including DPPH and ABTS scavenging rates,and better protective effect on CUR against gastric acid environment as well as longer release of CUR in simulated intestinal fluid.In addition,the HPPGAL-CUR delivery system possessed liver targeting property due to the existence of GAL,which could effectively alleviate the alcohol-induced liver damage and the inflammation indexes by inhibiting the oxidative stress.Therefore,HPP-GAL-CUR nanoparticles might be a potential candidate system for the prevention of alcoholic liver damage in the future.展开更多
Objective: To investigate the effect of Buzhong Yiqi decoction (补中益气汤, BZYQD) on liver damage induced by food allergy in mice. Methods: Nc/Jic strain mice with high levels of serum IgE were sensitized by ovalbumi...Objective: To investigate the effect of Buzhong Yiqi decoction (补中益气汤, BZYQD) on liver damage induced by food allergy in mice. Methods: Nc/Jic strain mice with high levels of serum IgE were sensitized by ovalbumin (OVA), and then divided into two groups and respectively treated with BZYQD (treated group) or normal saline (model group). Samples of serum, liver tissues and small intestine were collected two weeks later, and another group of non-sensitized mice was set as the normal group. The levels of serum alanine aminotransferase (ALT) were measured with spectrophotometry. The liver tissue and small intestine were stained with hematoxylin and eosin (HE) for pathologic analysis. The liver samples were also subjected to analysis of CD4-T helper cell and cytokine (interleukin-4, IL-4, interleukin-6, IL-6) expression with immunohistochemical (avidin-biotin complex, ABC) method. Results: Serum ALT levels decreased and obvious pathologic improvements were seen in the mice treated with BZYQD. And compared with the model mice, the number of positive cells of IL-4, IL-6 and CD4 cell decreased significantly in those treated with BZYQD. Conclusion: BZYQD can effectively decrease the production of cytokines associated with allergic reaction in the liver of mice thus effective in treating liver damage caused by food allergy.展开更多
Solanum Nigrum Linn,the purpose of this study was to characterize the chemical components of the extract of Solanum Nigrum Linn by LC-MS/MS,and to identify 29 compounds by positive and negative total ion flow maps.The...Solanum Nigrum Linn,the purpose of this study was to characterize the chemical components of the extract of Solanum Nigrum Linn by LC-MS/MS,and to identify 29 compounds by positive and negative total ion flow maps.The potential mechanism of action of Solanum Nigrum Linn in treating alcoholic liver injury was investigated by means of network pharmacology and molecular docking.A total of 288 component target genes and 1010 disease target genes were obtained,and 98 intersection targets and 7 core targets were obtained after the intersection of the two genes.GO analysis and KEGG analysis respectively obtained 20 signaling pathways such as anti-inflammation and anti-apoptosis.The results of molecular docking showed that the blood components could successfully dock with the target proteins of the disease such as GAPDH,IL6,SRC,EGFR and ESR1.This study provided a scientific basis for the development and application of Solanum Nigrum Linn.展开更多
The correlation of serum arylesterase(PON1) activity on phenylacetate determined by an integrated method to clas-sical biochemical indexes of liver damage was investigated for the use of PON1 activity to evaluate live...The correlation of serum arylesterase(PON1) activity on phenylacetate determined by an integrated method to clas-sical biochemical indexes of liver damage was investigated for the use of PON1 activity to evaluate liver damage.PON1 reaction curve as absorbance at 270 nm for 0.20 mmol/L phenylacetate hydrolysis was analyzed by the integrated method to determine maximal PON1 reaction rate.Classical biochemical indexes of liver damage were determined routinely.The 95% confidence threshold of PON1 activity in sera from healthy individuals was 2.12 mkat/L [(4.73±1.31) mkat/L,n=105].PON1 activity in clinical sera was closely correlated to serum albumin,total protein and the ratio of albumin to globulins,but was weakly correlated to both direct and total bilirubin in serum.There were no correlations of PON1 activity to γ-glutamyltransferase,alkaline phos-phatase,alanine aminotransferase and aspartate aminotransferase.Among 127 clinical sera with PON1 activity>2.12 mkat/L,there were 92% healthy individuals examined by albumin,90% healthy individuals examined by total protein,88% healthy individuals examined by total bilirubin,86% healthy individuals examined by direct bilirubin and 64% healthy individuals examined by the ratio of albumin to globulins,respectively.In each group of healthy individuals judged by classical biochemical indexes of close correlation to PON1 activity,percentage of healthy individuals examined by PON1 activity was always >80%.These results suggested PON1 activity on phenylacetate estimated by the integrated method was also suitable for the evaluation of liver damage.展开更多
The changes of hepatic hemodynamics and hemorrheology were investigated in dogs with acute liver damage inducted by acetaminophen There were remarkable disturtance in liver circulation and hemorrheological abnormality...The changes of hepatic hemodynamics and hemorrheology were investigated in dogs with acute liver damage inducted by acetaminophen There were remarkable disturtance in liver circulation and hemorrheological abnormality occuring in both slight and severe liver damage.The study indicated that the degree of disturbance in liver circulation as well as in lemorheological change is positively correlated with the severity of livei damage For example,marked increase in blood viscosity linked with elevated fibrinogen level appeared in slight liver damage,whereas reduced blood viscosity associated with decreased plasma fibrinogen level and hematocrit occured in severe liver damage.This study also revealed that the inciease of portal venous resistance(PVR)and the disturbance of liver circulation in slight liver damage were chiefly related to the increase of blood viscosity and the increase of PVR in severe liver damage was mainly associated with the reduction of the radius of porta vein.展开更多
Dengue fever is widespread in all tropical and subtropical areas of the world and is the main public health problem posed by arboviroses. In Burkina Faso, an outbreak of dengue serotype “DENV-2”, which is responsibl...Dengue fever is widespread in all tropical and subtropical areas of the world and is the main public health problem posed by arboviroses. In Burkina Faso, an outbreak of dengue serotype “DENV-2”, which is responsible for severe forms of dengue, has been reported. In this study, we will discuss liver damage during this disease. The aim of this study was to describe the sociodemographic, diagnostic, therapeutic and evolutionary aspects of dengue patients with hepatic cytolysis. Patients and Methods: This was a prospective cross-sectional study of dengue disease in 2 facilities in the city of Ouagadougou. The study was spread over a period of 3 months from August to November 2019. The study population consisted of all patients hospitalised for dengue with a positive AgNS1 and/or IgM rapid diagnostic test (RDT) and presenting signs of liver damage. Results: During our study period we recruited 134 patients with dengue fever of which 93 or 69.4% had at least one elevated transaminase. The sex ratio was 1.90 and the average age was 35 years. Symptoms of liver damage were rare with right hypochondrial pain in 4.30% of cases and jaundice in 1.07% of cases. Dengue haemorrhagic fever was found in 5 patients. IgG was negative in 77.42%. The majority of patients (44% or 47.31%) had at least one transaminase value elevated to the upper limit of normal (ULN);and a minority, 14 patients or 15.06%, had transaminases above 10 ULN. A small proportion of patients had hepatocellular failure 26.92% with a lowered prothrombin level. Ninety-four per cent (94.62%) of the patients received analgesics. Level 1 analgesic (paracetamol) was the most widely administered, particularly in 76 patients (86.36%). More than half of the patients (57.14%) had a length of stay of less than or equal to 3 days and the outcome was favourable in 91.40%. Conclusion: Dengue virus causes alterations in the liver parenchyma. The degree of liver damage is variable. As clinical symptoms are almost non-existent, the measurement of transaminases remains important.展开更多
Cyphostemma digitatum （Vitaceae） is a perennial, climbing, succulent undershrub with compound fleshy leaves and tendrils. The plant is used mainly as a food flavoring, but it is also a main constituent of traditiona...Cyphostemma digitatum （Vitaceae） is a perennial, climbing, succulent undershrub with compound fleshy leaves and tendrils. The plant is used mainly as a food flavoring, but it is also a main constituent of traditional Yemeni soup （Marak）. Besides that, it has been described to be used as a medicinal plant. The aim of this work was to study the hepatoprotective effect of the aqueous extract of C. digitatum against CCl4-induced liver injury in Guinea pigs. Animals were divided into four groups. Group I, served as normal control. Group II received 2 mL CCl4/kg b.w. diluted with olive oil, at 1：1 ratio on day 11. Group III （test group） was pre-treated orally with 100 mg/kg b.w. aqueous leaves extract of C. digitatum for 10 days followed by subcutaneous injection of CC14 （2 mL/kg b.w.）, once on day 11. Group IV were orally given Liv-52 （100 mg/kg b.w.） once daily for 10 days followed by subcutaneous injection of CC14. Our results show that, the activity of serum hepatic enzymes （alanine aminotranferase （ALT）, aspartate aminotranferase （AST）, and alkaline phosphatase （ALP）） were significantly elevated in Guinea pigs treated with CCl4, while both the C. digitatum extract and Liv-52 reduced significantly these enzymes activity. Also, the levels of glucose, urea, cholesterol and triglycerides were decreased when compared with intoxicated control. Histopathological examination of intoxicated animals showed fatty changes, inflammation and necrosis indicating liver damage, while the animals received C. digitatum or Liv-52 showed less pathological effects or normal liver when compared to animals treated with CC14 alone. Biochemical and histological results confirm the hepatoprotective effect of aqueous extract of C. digitatum.展开更多
The present study was performed to determine the influence of lipid peroxidation and perturbance of Ca2+ homeostasis on liver damage induced by 2-chloro-1, 3-butadiene (CBD) and the protective effects of vitamin E in ...The present study was performed to determine the influence of lipid peroxidation and perturbance of Ca2+ homeostasis on liver damage induced by 2-chloro-1, 3-butadiene (CBD) and the protective effects of vitamin E in Wistar rats. Animals were given intraperitoneally different doses (8,40 or 200 mg·kg-1 daily) of CBD for 21 days, and the following dose-dependent events were observed: liver damage, significant increase in liver lipid peroxides, and decreases in activities of erythrocytic glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). The pretreatment of rats with vitamin E (po 150 mg·kg-1) before administering CBD (iP 60 mg·kg-1 ) daily for 21 days prevented the following CBD-induced changes, the increase in serum cholylglycine (CG), hepatic LP, hepatic mitochondrion LP, hepatic oxidized glutathione (GSSG) (while the significant increase of reduced glutathione (GSH) was not affected) and the decrease in activities of erythrocytic SOD and hepatic mitochondrial calcium sequestration. These results suggest that lipid peroxidation and perturbance of Ca2+ homeostasis appear to contribute to the hepatotoxicity of CBD, and vitamin E might prevent the liver damage induced by CBD. The decrease in activities of GSH-Px and SOD in erythrocytes might be used as biomarkers for adverse effects of CBD on defense system against lipid peroxidation.展开更多
Objective: to clarify the value of combined detection of ALT, γ-GT and LAP in the early diagnosis of hyperthyroidism and liver damage. Methods: the research samples were selected from 200 patients with suspected hype...Objective: to clarify the value of combined detection of ALT, γ-GT and LAP in the early diagnosis of hyperthyroidism and liver damage. Methods: the research samples were selected from 200 patients with suspected hyperthyroidism and liver damage who were diagnosed and treated in our hospital from January 2020 to December 2021. All patients were subjected to combined detection of ALT, γ-GT and LAP indexes and pathological diagnosis. The results of physical diagnosis were listed as the control group, and the combined detection results of ALT, γ-GT and LAP indexes were listed as the observation group. Take the control group as the standard, the accuracy of the observation group and the ALT, γ-GT, γ-GT, and differences in LAP indicator levels. Results: taking the pathological diagnosis of the control group as the standard, the combined detection results of ALT, γ-GT and LAP indexes showed a sensitivity of -98.62% (143/145), a specificity of -98.21% (55/56), and an accuracy of -99.00% ( 198/200), and there were differences in the levels of ALT, γ-GT, and LAP between patients with hyperthyroidism and liver injury and patients with other diseases, and the differences were statistically significant (P<0.05). Conclusion: the combined detection of ALT, γ-GT and LAP in patients with hyperthyroidism and liver damage has high accuracy and significant clinical value.展开更多
Objective:Salt-processed Psoraleae Fructus(SPF)is widely used as a phytoestrogen-like agent in the treatment of osteoporosis.However,due to improper clinical use or misuse,resulting in liver damage.In this study,netwo...Objective:Salt-processed Psoraleae Fructus(SPF)is widely used as a phytoestrogen-like agent in the treatment of osteoporosis.However,due to improper clinical use or misuse,resulting in liver damage.In this study,network pharmacology was employed to analyze the mechanism of cholestatic liver damage.An adeno-associated virus overexpressing SULT1E1(rAAV8-SULT1E1)was constructed and the hepatotoxicity of SPF,psoralen,and isopsoralen was determined.Methods:By utilizing three databases inclding TCMSP,TCMID,and BATMAN-TCM,the targets of the three databases were summarized,and a total of 45 psoralen compounds were included.Network pharmacology analysis was then performed.The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo.SPF(10 g/kg),psoralen,and isopsoralen(50 mg/kg each)were intragastrically administered to mice for30 d.B-ultrasound and samples were collected and examined for follow-up experiments.Results:A total of 854 targets were predicted for 45 active components,with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF.A total of 126 pathways were enriched based on KEGG pathway analysis,with the"estrogen signaling pathway"identified as one of the top 20 pathways.In terms of pathological hepatic changes,treated mice had visually swollen hepatocytes,dilated bile ducts,and elevated serum biochemical markers,which were more prominent in mice treated with isopsoralen than in those treated with other compounds.Notably,the overexpression of SULT1E1 could reverse liver damage in each treatment group.B-ultrasound was used to observe the size of the gallbladder in vivo.The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-,psoralen-,and isopsoralen-treated groups,especially the SPF group.Compared with the expression levels in the negative control group(rAAV8-empty+con),the expression levels of FXR,Mrp2,Bsep,SULT1E1,SULT2A1,Ntcp,and Nrf2 decreased,whereas those of CYP7a1 and IL-6 increased in the SPF-,psoralen-,and isopsoralen-treated groups.Conclusion:The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators,indicating that SULT1E1 is an important target gene for SPF-induced liver damage.The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.展开更多
Introduction Ketamine is a phencyclidine derivative primarily used as an anesthetic and analgesic,playing a key role in the treatment of acute(perioperative)pain,chronic neuropathic pain,and therapy-resistant clinical...Introduction Ketamine is a phencyclidine derivative primarily used as an anesthetic and analgesic,playing a key role in the treatment of acute(perioperative)pain,chronic neuropathic pain,and therapy-resistant clinical depression.1 Although generally considered safe and effective for medical purposes,ketamine has rarely been reported to cause hepatotoxicity.However,due to its dissociative and hallucinogenic effects,recreational use—especially repeated administration—has led to an increased incidence of hepatotoxicity.展开更多
Objective To evaluate the protective effect of chlorogenic acid （CGA） on carbon tetrachloride （CCh）-induced liver injury of rats. Methods The anti-oxidative activity of CGA was investigated with several establishe...Objective To evaluate the protective effect of chlorogenic acid （CGA） on carbon tetrachloride （CCh）-induced liver injury of rats. Methods The anti-oxidative activity of CGA was investigated with several established in vitro systems. The hepatoprotective activity of CGA against CCI4-induced acute liver injury in eats was studied. The levels of alanine aminotranferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, and total bilirubin （TB） were measured. The histopathological examination was carried out to supplement the biochemical results. Results CGA possessed strong anti-oxidative ability in vitro. The CCh-induced liver toxicity experiment showed that the rats pretreated with CGA （300 or 500 mg/kg） had lower levels of ALT, AST, ALP, and TB than those of the CCI4-treated group. These data were supplemented with histopathological examination of rat liver sections. CGA did not show any mortality at the dose up to 5000 mg/kg. Conclusion CGAcould protect the liver againstCCI4-induced oxidative damage in rats, and the possible mechanism of the activity may be due to its free radical-scavenging and anti-oxidative activity.展开更多
Background： Morphine is commonly used to treat severe pain. This substance is significantly metabolized in the liver and causes disturbing effects. Genistein is an isoflavone and has antioxidant properties. The aim o...Background： Morphine is commonly used to treat severe pain. This substance is significantly metabolized in the liver and causes disturbing effects. Genistein is an isoflavone and has antioxidant properties. The aim of this study was to evaluate the effects of genistein against morphine damages on mouse liver. Methods： Between May 2017 and March 2018, 48 male mice were divided into six groups （n = 8 in each group）. Various doses of genistein （25 and 50 mg/kg） and morphine plus genistein （25 and 50 mg/kg） were administered intraperitoneally to 48 male mice for 20 consequent days. Aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, alkaline phosphatase （ALP）, serum nitric oxide （NO） levels, liver weight, and the diameter of hepatocytes and central hepatic vein were studied and compared using one-way analysis of variance. Results： Morphine administration significantly increased the mean diameter of the central hepatic vein （22.76 ± 1.9 μm vs. 15.04 ± 0.60μm, x^2= 21.814, P = 0.001） and hepatocytes （3.03 ± 0.10 μm vs. 1.10 ± 0.05 μm, x^2 = 9.873, P = 0.001） respectively, blood serum NO level （38.00% ± 2.09% vs. 18.72% ±4.40%, x^2 = 20.404, P 〈 0.001 ）, liver enzyme level （AST： 111.80 ± 5.10 ng/ml vs. 81.93 ±2.20 ng/ ml, x^2 = 32.201, P 〈 0.0001; ALT： 45.14 ± 4.10 ng/ml vs. 35.49 ± 2.50 ng/ml, x^2= 18.203, P 〈 0.0001; and ALP： 3.28 ± 0.20 ng/ml vs. 2.14± 0.10, x^2= 5.04, P 〈 0.0001, respectively）, and decreased liver weight （18.50 ± 0.90 g vs. 27.15 ± 0.50 g, x^2 = 22.415, P=0.001 ） compared to saline group （0.535±3.750, P 〈 0.0001）. However, administration of genistein plus morphine significantly enhanced liver weight （25 mg/kg： 21.15 ±2.13 g vs. 18.50 ±0.90 g, x^2= 19.251 P 〈 0.0001 ; 50 mg/kg： 21.20 ±1.00 g vs. 18.5± 0.9 g, x^2= 19.502, P 〈 0.0001, respectively） and reduced the mean diameter of hepatocyte （25 mg/kg： 2.17±0.30 μm vs. 3.03 ± 0.10 μm, x^2 = 22.780, P =0.001 ; 50 mg/kg： 2.01± 0.20 μm vs. 3.03 ±0.10 μm x^2 = 7.120, P = 0.001, respectively）, central hepatic vein （25 mg/kg： 19.53 ± 1.00 μm vs. 22.76 ±1.90 μm, x^2= 20.681, P = 0.001; 50 mg/kg： 19.44 ± 1.20 μm vs. 22.76 ± 1.90 μm, x^2 = 18.451, P = 0.001, respectively）, AST （25 mg/kg： 95.40 ± 5.20 ng/ml vs. 111.80 ±5.010 ng/ml, P 〈 0.0001：50 mg/kg： 90.78 ± 6.00 ng/ml vs. 111.80 ± 5.10 ng/ml, x^2= 17.112, P 〈 0.0001, respectively）, ALT （25 mg/kg： 35.78 ± 5.01 ng/ml vs. 45.14 ± 4.10 ng/ml, x^2= 15.320, P 〈 0.0001 ; 50 mg/kg： 33.78±2.60ng/mlvs. 45.14±4.10ng/ml,x^2= 14.023, P〈0.0001,respectively）,ALP（25mg/kg：2.35±0.30ng/mlvs. 3.28±0.20ng/ml, x^2=4.101, P 〈 0.0001; 50 mg/kg： 2.34 ± 0.10 ng/ml vs. 3.28 ± 0.20 ng/ml, x^2=2.033, P 〈 0.0001, respectively）, and NO levels （25 mg/ kg： 25.92% ± 2.30% vs. 38% ± 2.09%, x^2= 17.103, P 〈 0.0001 ; 50 mg/kg： 24.74% ± 4.10% vs. 38% ± 2.09%, x^2 = 25.050, P - 0.001, respectively） compared to morphine group. Conclusion： It seems that genistein administration might improve liver damages induced by morphine in mice.展开更多
AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and repair.METHODS Rats received intraperitoneal injection of the hepatotoxin thio...AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and repair.METHODS Rats received intraperitoneal injection of the hepatotoxin thioacetamide(TAA), and were sacrificed regularly between 1 and 96 h thereafter. Serum levels of transaminases and iron were measured using conventional laboratory assays. Liver tissue was used for conventional histology, immunohistology, and iron staining. The expression of acute-phase cytokines, ferritin light chain(FTL), and ferritin heavy chain(FTH)was investigated in the liver by q RT-PCR. Western blotting was used to investigate FTL and FTH in liver tissue and serum. Liver and spleen tissue was also used to determine iron concentrations.RESULTS After a short initial decrease, iron serum concentrations increased in parallel with serum transaminase(aspartate aminotransferase and alanine aminotransferase) levels, which reached a maximum at 48 h, and decreased thereafter. Similarly, after 48 h a significant increase in FTL, and after 72 h in FTH was detected in serum. While earliest morphological signs of inflammation in liver were visible after 6 h, increased expression of the two acute-phase cytokines IFN-γ(1 h) and IL-1β(3 h) was detectable earlier, with maximum values after 12-24 h. Iron concentrations in liver tissue increased steadily between 1 h and 48 h, and remained high at 96 h. In contrast, spleen iron concentrations remained unchanged until 48 h, and increased mildly thereafter(96 h). Although tissue iron staining was negative, hepatic FTL and FTH protein levels were strongly elevated. Our results reveal effects on hepatic iron concentrations after direct liver injury by TAA. The increase of liver iron concentrations may be due to the uptake of a significant proportion of the metal by healthy hepatocytes, and only to a minor extent by macrophages, as spleen iron concentrations do not increase in parallel. The temporary increase of iron, FTH and transaminases in serum is obviously due to their release by damaged hepatocytes.CONCLUSION Increased liver iron levels may be the consequence of hepatocyte damage. Iron released into serum by damaged hepatocytes is obviously transported back and stored via ferritins.展开更多
Cafeteria diet is known to induce excessive endoplasmic reticulum stress(ERS),oxidative stress(OS),and inflammation that could cause metabolic changes and liver diseases.Bergamottin(BGM)is a natural furanocoumarin tha...Cafeteria diet is known to induce excessive endoplasmic reticulum stress(ERS),oxidative stress(OS),and inflammation that could cause metabolic changes and liver diseases.Bergamottin(BGM)is a natural furanocoumarin that is known to have various biological activities.The present study,for the first time,assessed the reducing effect of BGM on the development of liver damage in cafeteria diet fed mice.48 male C57BL/6 mice were fed an experimental diets diet for 16 weeks and BGM(0.05 mg/kg and 0.22 mg/kg)was administered for the last four weeks.The serum samples and liver homogenates were assessed for markers of ERS,OS,and inflammation.Also,histopathological analyzes were performed.This study demonstrated that the CAF diet caused metabolic changes,ERS,OS,and inflammation in serum and liver tissue.However,BGM exerts anti-oxidant,anti-ER stress anti-inflammatory effects in CAF-induced liver damage.Therefore,BGM may potentially be a novel therapeutic compound to ameliorate liver damage.展开更多
文摘AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver damage,which was confirmed by liver histology.In addition,HL combined with I/R also caused significantly increased hepatocyte apoptosis,as evidenced by increased TUNEL-positive cells(6.20 ± 0.29 vs 1.5 ± 0.22,4.47 ± 0.45 or 1.97 ± 0.47,P < 0.01),elevated expression of caspase-3 and lower expression of bcl-2.Furthermore,when compared to HL or I/R alone,HL plus I/R enhanced serum TNF-,IL-1,liver mitochondrial MDA and Ca 2+ levels,suppressed SOD and GSH-Px in liver mitochondria,and markedly up-regulated the activity(11.76 ± 2.36 vs 4.77 ± 2.31 or 3.11 ± 1.35,P < 0.01) and expression(3.24 ± 0.38 vs 1.98 ± 0.88 or 1.72 ± 0.58,P < 0.01) of CYP2E1 in liver.CONCLUSION:The coexistence of HL and acute cerebral I/R induces severe liver damage,suggesting that cerebral ischemic stroke would exaggerate the damage of liver caused by HL.This effect is possibly due to en-hanced CYP2E1 induction which further promotes oxidative damage,inflammation and hepatocyte apoptosis.
文摘AIM: To evaluate the effects of extrahepatic collaterals to the liver on liver damage and patient outcome after embolotherapy for the ruptured hepatic artery pseudoa- neurysm following hepatobiliary pancreatic surgery. METHODS: We reviewed 9 patients who underwent transcatheter arterial embolization (TAE) for the ruptured hepatic artery pseudoaneurysm following major hepato- biliary pancreatic surgery between June 1992 and April 2006. We paid special attention to the extrahepatic arte- rial collaterals to the liver which may affect post-TAE liver damage and patient outcome. RESULTS: The underlying diseases were all malignan- cies, and the surgical procedures included hepatopancre- atoduodenectomy in 2 patients, hepatic resection with removal of the bile duct in 5, and pancreaticoduodenec- tomy in 2. A total of 11 pseudoaneurysm developed: 4 in the common hepatic artery, 4 in the proper hepatic artery, and 3 in the right hepatic artery. Successful he- mostasis was accomplished with the initial TAE in all patients, except for 1. Extrahepatic arterial pathways to the liver, including the right inferior phrenic artery, the jejunal branches, and the aberrant left hepatic artery, were identified in 8 of the 9 patients after the completion of TAE. The development of collaterals depended on the extent of liver mobilization during the hepatic resection, the postoperative period, the presence or absence of an aberrant left hepatic artery, and the concomitant arte- rial stenosis adjacent to the pseudoaneurysm. The liver tolerated TAE without significant consequences when at least one of the collaterals from the inferior phrenic ar-tery or the aberrant left hepatic artery was present. One patient, however, with no extrahepatic collaterals died of liver failure due to total liver necrosis 9 d after TAE. CONCLUSION: When TAE is performed on ruptured hepatic artery pseudoaneurysm, reduced collateral path- ways to the liver created by the primary surgical proce- dure and a short postoperative interval may lead to an unfavorable outcome.
基金This work was financially supported by the Special Fund Project for Technological Innovation of Fujian Agriculture and Forestry University(CXZX2019055G)the Science and Technology Project on Social Development of Cixi(CN2020027).
文摘This study explored the therapeutic effects of Auricularia auricula melanin(AAM)on alcoholic liver damage in vitro and in vivo.Human normal liver L02 cells were pre-treated with ethanol and then treated with AAM to explore the therapeutic effect of AAM on ethanol-induced hepatocyte injury.The results show that AAM signifi cantly elevated the cell viability,ameliorated the cell morphology,reduced the ROS and increased the GSH/GSSG of ethanol-pretreated L02 cells.Then,mice were administered with ethanol to induce acute alcoholic liver damage,and administered with AAM to further study the therapeutic effect of AAM on alcoholic liver damage in mice.As a result,AAM reduced the levels of ALT,AST,TG,and MDA,increased the levels of ADH,SOD,and CAT in liver damage mice.The therapeutic effect of AAM may be related to inhibition of CYP2E1 expression and activation of Nrf2 and its downstream antioxidase.The research enriched the bioactivity of AAM and provided some ideas for the development of melanin-related health foods.
文摘AIM： To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan （GB34） on CCl4-induced chronic liver damage in rats. METHODS： Rats were injected intraperitoneally with CCh （1 mL/kg） and treated with manual acupuncture using reinforcing manipulation techniques at left GB34 （Yanglingquan） 3 times a week for 10 wk. A nonacupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index, biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted. RESULTS： Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes. CONCLUSION： Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCh-intoxicated rats.
文摘AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS After staphylococcal enterotoxin B(SEB ) mixed with D--galactosamine (D-GaiN )were injected intraperitoneally into Balb/c miceand those previously treated with cyclosporin A,blood samples were collected and livers wereisolated at 2, 6, 12 and 24 h. Patterns othepatocellular death were studiedmorphologically and biochemically, circulatingcytokines (TNF-a, IFN--y ) and mice mortalitywithin 24h was assessed.RESU’LTS The SEB could induce the typicalapoptotic changes of hepatocytes, the D-GaiNcould induce hepatocytes apoptosis anddegeneration at the same time, and the micehaving received the SEB + D-GaiN injectionsdeveloped apoptosis at 2 and 6 h, but after 12 hhepatocytes were characterized by severein jury, whereas all the examinations in thecyclosporin A treated mice were normal.CONCLUSION Hepatic cell apoptosis might berelated to necrosis, and massive hepatocyteapoptosis is likely the initiating step of acutehepatic necrosis in mice. The effects induced bySEB and D--GaiN on hepatocytes might bemediated by T cells, and could be prevented bycyclosporin A.
基金supported by the National Key Research and Development Program of China(2022YFF1100205)the National Natural Science Foundation of China(31972105)the National Science Fund for Distinguished Young Scholars of China(31925031).
文摘The aim of this study is to investigate the feasibility of Maillard reaction products of Haematococcus pluvialis protein and galactose(HPP-GAL)for improving the bioactivities of curcumin(CUR)for alleviating alcoholic liver damage.CUR was embedded into HPP-GAL nanoparticles by the self-assembly of hydrogen bonding and hydrophobic interaction with the particle size around 200 nm.HPP-GAL enhanced the encapsulation efficiency and loading amount of CUR with the value of(89.21±0.33)%and(0.500±0.004)%,respectively.The stabilities of CUR under strong acid,salt ion stability and ultraviolet irradiation conditions were improved by the encapsulation.HPP-GAL-CUR nanoparticles exhibited excellent concentration-dependent in vitro antioxidant activities including DPPH and ABTS scavenging rates,and better protective effect on CUR against gastric acid environment as well as longer release of CUR in simulated intestinal fluid.In addition,the HPPGAL-CUR delivery system possessed liver targeting property due to the existence of GAL,which could effectively alleviate the alcohol-induced liver damage and the inflammation indexes by inhibiting the oxidative stress.Therefore,HPP-GAL-CUR nanoparticles might be a potential candidate system for the prevention of alcoholic liver damage in the future.
文摘Objective: To investigate the effect of Buzhong Yiqi decoction (补中益气汤, BZYQD) on liver damage induced by food allergy in mice. Methods: Nc/Jic strain mice with high levels of serum IgE were sensitized by ovalbumin (OVA), and then divided into two groups and respectively treated with BZYQD (treated group) or normal saline (model group). Samples of serum, liver tissues and small intestine were collected two weeks later, and another group of non-sensitized mice was set as the normal group. The levels of serum alanine aminotransferase (ALT) were measured with spectrophotometry. The liver tissue and small intestine were stained with hematoxylin and eosin (HE) for pathologic analysis. The liver samples were also subjected to analysis of CD4-T helper cell and cytokine (interleukin-4, IL-4, interleukin-6, IL-6) expression with immunohistochemical (avidin-biotin complex, ABC) method. Results: Serum ALT levels decreased and obvious pathologic improvements were seen in the mice treated with BZYQD. And compared with the model mice, the number of positive cells of IL-4, IL-6 and CD4 cell decreased significantly in those treated with BZYQD. Conclusion: BZYQD can effectively decrease the production of cytokines associated with allergic reaction in the liver of mice thus effective in treating liver damage caused by food allergy.
文摘Solanum Nigrum Linn,the purpose of this study was to characterize the chemical components of the extract of Solanum Nigrum Linn by LC-MS/MS,and to identify 29 compounds by positive and negative total ion flow maps.The potential mechanism of action of Solanum Nigrum Linn in treating alcoholic liver injury was investigated by means of network pharmacology and molecular docking.A total of 288 component target genes and 1010 disease target genes were obtained,and 98 intersection targets and 7 core targets were obtained after the intersection of the two genes.GO analysis and KEGG analysis respectively obtained 20 signaling pathways such as anti-inflammation and anti-apoptosis.The results of molecular docking showed that the blood components could successfully dock with the target proteins of the disease such as GAPDH,IL6,SRC,EGFR and ESR1.This study provided a scientific basis for the development and application of Solanum Nigrum Linn.
基金Project (No. 30200266) supported by the National Natural Science Foundation of China
文摘The correlation of serum arylesterase(PON1) activity on phenylacetate determined by an integrated method to clas-sical biochemical indexes of liver damage was investigated for the use of PON1 activity to evaluate liver damage.PON1 reaction curve as absorbance at 270 nm for 0.20 mmol/L phenylacetate hydrolysis was analyzed by the integrated method to determine maximal PON1 reaction rate.Classical biochemical indexes of liver damage were determined routinely.The 95% confidence threshold of PON1 activity in sera from healthy individuals was 2.12 mkat/L [(4.73±1.31) mkat/L,n=105].PON1 activity in clinical sera was closely correlated to serum albumin,total protein and the ratio of albumin to globulins,but was weakly correlated to both direct and total bilirubin in serum.There were no correlations of PON1 activity to γ-glutamyltransferase,alkaline phos-phatase,alanine aminotransferase and aspartate aminotransferase.Among 127 clinical sera with PON1 activity>2.12 mkat/L,there were 92% healthy individuals examined by albumin,90% healthy individuals examined by total protein,88% healthy individuals examined by total bilirubin,86% healthy individuals examined by direct bilirubin and 64% healthy individuals examined by the ratio of albumin to globulins,respectively.In each group of healthy individuals judged by classical biochemical indexes of close correlation to PON1 activity,percentage of healthy individuals examined by PON1 activity was always >80%.These results suggested PON1 activity on phenylacetate estimated by the integrated method was also suitable for the evaluation of liver damage.
文摘The changes of hepatic hemodynamics and hemorrheology were investigated in dogs with acute liver damage inducted by acetaminophen There were remarkable disturtance in liver circulation and hemorrheological abnormality occuring in both slight and severe liver damage.The study indicated that the degree of disturbance in liver circulation as well as in lemorheological change is positively correlated with the severity of livei damage For example,marked increase in blood viscosity linked with elevated fibrinogen level appeared in slight liver damage,whereas reduced blood viscosity associated with decreased plasma fibrinogen level and hematocrit occured in severe liver damage.This study also revealed that the inciease of portal venous resistance(PVR)and the disturbance of liver circulation in slight liver damage were chiefly related to the increase of blood viscosity and the increase of PVR in severe liver damage was mainly associated with the reduction of the radius of porta vein.
文摘Dengue fever is widespread in all tropical and subtropical areas of the world and is the main public health problem posed by arboviroses. In Burkina Faso, an outbreak of dengue serotype “DENV-2”, which is responsible for severe forms of dengue, has been reported. In this study, we will discuss liver damage during this disease. The aim of this study was to describe the sociodemographic, diagnostic, therapeutic and evolutionary aspects of dengue patients with hepatic cytolysis. Patients and Methods: This was a prospective cross-sectional study of dengue disease in 2 facilities in the city of Ouagadougou. The study was spread over a period of 3 months from August to November 2019. The study population consisted of all patients hospitalised for dengue with a positive AgNS1 and/or IgM rapid diagnostic test (RDT) and presenting signs of liver damage. Results: During our study period we recruited 134 patients with dengue fever of which 93 or 69.4% had at least one elevated transaminase. The sex ratio was 1.90 and the average age was 35 years. Symptoms of liver damage were rare with right hypochondrial pain in 4.30% of cases and jaundice in 1.07% of cases. Dengue haemorrhagic fever was found in 5 patients. IgG was negative in 77.42%. The majority of patients (44% or 47.31%) had at least one transaminase value elevated to the upper limit of normal (ULN);and a minority, 14 patients or 15.06%, had transaminases above 10 ULN. A small proportion of patients had hepatocellular failure 26.92% with a lowered prothrombin level. Ninety-four per cent (94.62%) of the patients received analgesics. Level 1 analgesic (paracetamol) was the most widely administered, particularly in 76 patients (86.36%). More than half of the patients (57.14%) had a length of stay of less than or equal to 3 days and the outcome was favourable in 91.40%. Conclusion: Dengue virus causes alterations in the liver parenchyma. The degree of liver damage is variable. As clinical symptoms are almost non-existent, the measurement of transaminases remains important.
文摘Cyphostemma digitatum （Vitaceae） is a perennial, climbing, succulent undershrub with compound fleshy leaves and tendrils. The plant is used mainly as a food flavoring, but it is also a main constituent of traditional Yemeni soup （Marak）. Besides that, it has been described to be used as a medicinal plant. The aim of this work was to study the hepatoprotective effect of the aqueous extract of C. digitatum against CCl4-induced liver injury in Guinea pigs. Animals were divided into four groups. Group I, served as normal control. Group II received 2 mL CCl4/kg b.w. diluted with olive oil, at 1：1 ratio on day 11. Group III （test group） was pre-treated orally with 100 mg/kg b.w. aqueous leaves extract of C. digitatum for 10 days followed by subcutaneous injection of CC14 （2 mL/kg b.w.）, once on day 11. Group IV were orally given Liv-52 （100 mg/kg b.w.） once daily for 10 days followed by subcutaneous injection of CC14. Our results show that, the activity of serum hepatic enzymes （alanine aminotranferase （ALT）, aspartate aminotranferase （AST）, and alkaline phosphatase （ALP）） were significantly elevated in Guinea pigs treated with CCl4, while both the C. digitatum extract and Liv-52 reduced significantly these enzymes activity. Also, the levels of glucose, urea, cholesterol and triglycerides were decreased when compared with intoxicated control. Histopathological examination of intoxicated animals showed fatty changes, inflammation and necrosis indicating liver damage, while the animals received C. digitatum or Liv-52 showed less pathological effects or normal liver when compared to animals treated with CC14 alone. Biochemical and histological results confirm the hepatoprotective effect of aqueous extract of C. digitatum.
文摘The present study was performed to determine the influence of lipid peroxidation and perturbance of Ca2+ homeostasis on liver damage induced by 2-chloro-1, 3-butadiene (CBD) and the protective effects of vitamin E in Wistar rats. Animals were given intraperitoneally different doses (8,40 or 200 mg·kg-1 daily) of CBD for 21 days, and the following dose-dependent events were observed: liver damage, significant increase in liver lipid peroxides, and decreases in activities of erythrocytic glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). The pretreatment of rats with vitamin E (po 150 mg·kg-1) before administering CBD (iP 60 mg·kg-1 ) daily for 21 days prevented the following CBD-induced changes, the increase in serum cholylglycine (CG), hepatic LP, hepatic mitochondrion LP, hepatic oxidized glutathione (GSSG) (while the significant increase of reduced glutathione (GSH) was not affected) and the decrease in activities of erythrocytic SOD and hepatic mitochondrial calcium sequestration. These results suggest that lipid peroxidation and perturbance of Ca2+ homeostasis appear to contribute to the hepatotoxicity of CBD, and vitamin E might prevent the liver damage induced by CBD. The decrease in activities of GSH-Px and SOD in erythrocytes might be used as biomarkers for adverse effects of CBD on defense system against lipid peroxidation.
文摘Objective: to clarify the value of combined detection of ALT, γ-GT and LAP in the early diagnosis of hyperthyroidism and liver damage. Methods: the research samples were selected from 200 patients with suspected hyperthyroidism and liver damage who were diagnosed and treated in our hospital from January 2020 to December 2021. All patients were subjected to combined detection of ALT, γ-GT and LAP indexes and pathological diagnosis. The results of physical diagnosis were listed as the control group, and the combined detection results of ALT, γ-GT and LAP indexes were listed as the observation group. Take the control group as the standard, the accuracy of the observation group and the ALT, γ-GT, γ-GT, and differences in LAP indicator levels. Results: taking the pathological diagnosis of the control group as the standard, the combined detection results of ALT, γ-GT and LAP indexes showed a sensitivity of -98.62% (143/145), a specificity of -98.21% (55/56), and an accuracy of -99.00% ( 198/200), and there were differences in the levels of ALT, γ-GT, and LAP between patients with hyperthyroidism and liver injury and patients with other diseases, and the differences were statistically significant (P<0.05). Conclusion: the combined detection of ALT, γ-GT and LAP in patients with hyperthyroidism and liver damage has high accuracy and significant clinical value.
基金supported by the National Natural Science Foundation of China(81973484 and 82304736)the 2022 Natural Science Foundation of Nanjing University of Chinese Medicine(XZR2021085)。
文摘Objective:Salt-processed Psoraleae Fructus(SPF)is widely used as a phytoestrogen-like agent in the treatment of osteoporosis.However,due to improper clinical use or misuse,resulting in liver damage.In this study,network pharmacology was employed to analyze the mechanism of cholestatic liver damage.An adeno-associated virus overexpressing SULT1E1(rAAV8-SULT1E1)was constructed and the hepatotoxicity of SPF,psoralen,and isopsoralen was determined.Methods:By utilizing three databases inclding TCMSP,TCMID,and BATMAN-TCM,the targets of the three databases were summarized,and a total of 45 psoralen compounds were included.Network pharmacology analysis was then performed.The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo.SPF(10 g/kg),psoralen,and isopsoralen(50 mg/kg each)were intragastrically administered to mice for30 d.B-ultrasound and samples were collected and examined for follow-up experiments.Results:A total of 854 targets were predicted for 45 active components,with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF.A total of 126 pathways were enriched based on KEGG pathway analysis,with the"estrogen signaling pathway"identified as one of the top 20 pathways.In terms of pathological hepatic changes,treated mice had visually swollen hepatocytes,dilated bile ducts,and elevated serum biochemical markers,which were more prominent in mice treated with isopsoralen than in those treated with other compounds.Notably,the overexpression of SULT1E1 could reverse liver damage in each treatment group.B-ultrasound was used to observe the size of the gallbladder in vivo.The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-,psoralen-,and isopsoralen-treated groups,especially the SPF group.Compared with the expression levels in the negative control group(rAAV8-empty+con),the expression levels of FXR,Mrp2,Bsep,SULT1E1,SULT2A1,Ntcp,and Nrf2 decreased,whereas those of CYP7a1 and IL-6 increased in the SPF-,psoralen-,and isopsoralen-treated groups.Conclusion:The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators,indicating that SULT1E1 is an important target gene for SPF-induced liver damage.The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.
文摘Introduction Ketamine is a phencyclidine derivative primarily used as an anesthetic and analgesic,playing a key role in the treatment of acute(perioperative)pain,chronic neuropathic pain,and therapy-resistant clinical depression.1 Although generally considered safe and effective for medical purposes,ketamine has rarely been reported to cause hepatotoxicity.However,due to its dissociative and hallucinogenic effects,recreational use—especially repeated administration—has led to an increased incidence of hepatotoxicity.
基金National Basic Research Program of China(2012CB724001)
文摘Objective To evaluate the protective effect of chlorogenic acid （CGA） on carbon tetrachloride （CCh）-induced liver injury of rats. Methods The anti-oxidative activity of CGA was investigated with several established in vitro systems. The hepatoprotective activity of CGA against CCI4-induced acute liver injury in eats was studied. The levels of alanine aminotranferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, and total bilirubin （TB） were measured. The histopathological examination was carried out to supplement the biochemical results. Results CGA possessed strong anti-oxidative ability in vitro. The CCh-induced liver toxicity experiment showed that the rats pretreated with CGA （300 or 500 mg/kg） had lower levels of ALT, AST, ALP, and TB than those of the CCI4-treated group. These data were supplemented with histopathological examination of rat liver sections. CGA did not show any mortality at the dose up to 5000 mg/kg. Conclusion CGAcould protect the liver againstCCI4-induced oxidative damage in rats, and the possible mechanism of the activity may be due to its free radical-scavenging and anti-oxidative activity.
文摘Background： Morphine is commonly used to treat severe pain. This substance is significantly metabolized in the liver and causes disturbing effects. Genistein is an isoflavone and has antioxidant properties. The aim of this study was to evaluate the effects of genistein against morphine damages on mouse liver. Methods： Between May 2017 and March 2018, 48 male mice were divided into six groups （n = 8 in each group）. Various doses of genistein （25 and 50 mg/kg） and morphine plus genistein （25 and 50 mg/kg） were administered intraperitoneally to 48 male mice for 20 consequent days. Aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, alkaline phosphatase （ALP）, serum nitric oxide （NO） levels, liver weight, and the diameter of hepatocytes and central hepatic vein were studied and compared using one-way analysis of variance. Results： Morphine administration significantly increased the mean diameter of the central hepatic vein （22.76 ± 1.9 μm vs. 15.04 ± 0.60μm, x^2= 21.814, P = 0.001） and hepatocytes （3.03 ± 0.10 μm vs. 1.10 ± 0.05 μm, x^2 = 9.873, P = 0.001） respectively, blood serum NO level （38.00% ± 2.09% vs. 18.72% ±4.40%, x^2 = 20.404, P 〈 0.001 ）, liver enzyme level （AST： 111.80 ± 5.10 ng/ml vs. 81.93 ±2.20 ng/ ml, x^2 = 32.201, P 〈 0.0001; ALT： 45.14 ± 4.10 ng/ml vs. 35.49 ± 2.50 ng/ml, x^2= 18.203, P 〈 0.0001; and ALP： 3.28 ± 0.20 ng/ml vs. 2.14± 0.10, x^2= 5.04, P 〈 0.0001, respectively）, and decreased liver weight （18.50 ± 0.90 g vs. 27.15 ± 0.50 g, x^2 = 22.415, P=0.001 ） compared to saline group （0.535±3.750, P 〈 0.0001）. However, administration of genistein plus morphine significantly enhanced liver weight （25 mg/kg： 21.15 ±2.13 g vs. 18.50 ±0.90 g, x^2= 19.251 P 〈 0.0001 ; 50 mg/kg： 21.20 ±1.00 g vs. 18.5± 0.9 g, x^2= 19.502, P 〈 0.0001, respectively） and reduced the mean diameter of hepatocyte （25 mg/kg： 2.17±0.30 μm vs. 3.03 ± 0.10 μm, x^2 = 22.780, P =0.001 ; 50 mg/kg： 2.01± 0.20 μm vs. 3.03 ±0.10 μm x^2 = 7.120, P = 0.001, respectively）, central hepatic vein （25 mg/kg： 19.53 ± 1.00 μm vs. 22.76 ±1.90 μm, x^2= 20.681, P = 0.001; 50 mg/kg： 19.44 ± 1.20 μm vs. 22.76 ± 1.90 μm, x^2 = 18.451, P = 0.001, respectively）, AST （25 mg/kg： 95.40 ± 5.20 ng/ml vs. 111.80 ±5.010 ng/ml, P 〈 0.0001：50 mg/kg： 90.78 ± 6.00 ng/ml vs. 111.80 ± 5.10 ng/ml, x^2= 17.112, P 〈 0.0001, respectively）, ALT （25 mg/kg： 35.78 ± 5.01 ng/ml vs. 45.14 ± 4.10 ng/ml, x^2= 15.320, P 〈 0.0001 ; 50 mg/kg： 33.78±2.60ng/mlvs. 45.14±4.10ng/ml,x^2= 14.023, P〈0.0001,respectively）,ALP（25mg/kg：2.35±0.30ng/mlvs. 3.28±0.20ng/ml, x^2=4.101, P 〈 0.0001; 50 mg/kg： 2.34 ± 0.10 ng/ml vs. 3.28 ± 0.20 ng/ml, x^2=2.033, P 〈 0.0001, respectively）, and NO levels （25 mg/ kg： 25.92% ± 2.30% vs. 38% ± 2.09%, x^2= 17.103, P 〈 0.0001 ; 50 mg/kg： 24.74% ± 4.10% vs. 38% ± 2.09%, x^2 = 25.050, P - 0.001, respectively） compared to morphine group. Conclusion： It seems that genistein administration might improve liver damages induced by morphine in mice.
基金Support by the German Research Foundationthe Open Access Publication Funds of the Gottingen University
文摘AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and repair.METHODS Rats received intraperitoneal injection of the hepatotoxin thioacetamide(TAA), and were sacrificed regularly between 1 and 96 h thereafter. Serum levels of transaminases and iron were measured using conventional laboratory assays. Liver tissue was used for conventional histology, immunohistology, and iron staining. The expression of acute-phase cytokines, ferritin light chain(FTL), and ferritin heavy chain(FTH)was investigated in the liver by q RT-PCR. Western blotting was used to investigate FTL and FTH in liver tissue and serum. Liver and spleen tissue was also used to determine iron concentrations.RESULTS After a short initial decrease, iron serum concentrations increased in parallel with serum transaminase(aspartate aminotransferase and alanine aminotransferase) levels, which reached a maximum at 48 h, and decreased thereafter. Similarly, after 48 h a significant increase in FTL, and after 72 h in FTH was detected in serum. While earliest morphological signs of inflammation in liver were visible after 6 h, increased expression of the two acute-phase cytokines IFN-γ(1 h) and IL-1β(3 h) was detectable earlier, with maximum values after 12-24 h. Iron concentrations in liver tissue increased steadily between 1 h and 48 h, and remained high at 96 h. In contrast, spleen iron concentrations remained unchanged until 48 h, and increased mildly thereafter(96 h). Although tissue iron staining was negative, hepatic FTL and FTH protein levels were strongly elevated. Our results reveal effects on hepatic iron concentrations after direct liver injury by TAA. The increase of liver iron concentrations may be due to the uptake of a significant proportion of the metal by healthy hepatocytes, and only to a minor extent by macrophages, as spleen iron concentrations do not increase in parallel. The temporary increase of iron, FTH and transaminases in serum is obviously due to their release by damaged hepatocytes.CONCLUSION Increased liver iron levels may be the consequence of hepatocyte damage. Iron released into serum by damaged hepatocytes is obviously transported back and stored via ferritins.
基金This work was supported by Office of Scientific Research Projects of Karadeniz Technical University under Project number:TDK-2021-9315.
文摘Cafeteria diet is known to induce excessive endoplasmic reticulum stress(ERS),oxidative stress(OS),and inflammation that could cause metabolic changes and liver diseases.Bergamottin(BGM)is a natural furanocoumarin that is known to have various biological activities.The present study,for the first time,assessed the reducing effect of BGM on the development of liver damage in cafeteria diet fed mice.48 male C57BL/6 mice were fed an experimental diets diet for 16 weeks and BGM(0.05 mg/kg and 0.22 mg/kg)was administered for the last four weeks.The serum samples and liver homogenates were assessed for markers of ERS,OS,and inflammation.Also,histopathological analyzes were performed.This study demonstrated that the CAF diet caused metabolic changes,ERS,OS,and inflammation in serum and liver tissue.However,BGM exerts anti-oxidant,anti-ER stress anti-inflammatory effects in CAF-induced liver damage.Therefore,BGM may potentially be a novel therapeutic compound to ameliorate liver damage.
