Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

No significant increases in serum SDH, ALT and AST activities were observed in goats and rats receiving oral sulfadimethoxine at 5 times the therapeutic dose. The quail showed significantly higher activities of SDH and ALT when compared to control values. Moderate increases in liver microsomal cytochrome P-450 and aniline hydroxylase activity were observed in goats and quail but no appreciable change in benzphetamine N-demethylase activity was detected in any species. These results suggest a lack of hepatic toxicity of sulfadimethoxine to these species under the reported experimental conditions.
 ...
PMID:Studies on possible sulfadimethoxine toxicity to liver and liver drug metabolizing enzyme system of goats, quail and rats. 327 41

The effects of subclinical fasciolosis at various stages of its development on bile flow and bile acid secretion and on the hepatobiliary transport of bilirubin were investigated in experimentally infected sheep. Bile flow was significantly reduced by weeks 6-14 postinfection. This was accompanied by a decrease in bile acid secretion by weeks 6-8. Serum AST and GLDH activities and serum bile acid concentration were significantly elevated from weeks 6 to 14. Total serum bilirubin was maximally increased at 6 weeks postinfection and remained elevated at weeks 8 and 14. Increases corresponded to both unconjugated and conjugated fractions, although the conjugated/total bilirubin ratio was enhanced in all infected animals. Biliary bilirubin secretion declined from weeks 6 to 14. No alteration was detected in either uridine diphosphate (UDP)-glucuronosyltransferase activity, cytochrome P-450 concentration, or hematological markers of hemolysis. This study shows that the migration of immature flukes in the course of ovine fasciolosis causes a cholestatic phenomenon responsible for changes in serum and biliary bilirubin levels.
 ...
PMID:The effects of subclinical fasciolosis on hepatic secretory function in sheep. 773 19

Acetaminophen high doses toxicity has been reported in clinical and experimental studies in relation with cytochrome P-450. (Acetaminophen metabolite). Thinking that biliary tract obstructions hould increases drugs toxicity because interferes toxic substances excretion or it modify the activity of P-450 we decided to study acetaminophen toxicity in rats with biliary tract obstruction. Male sprague Dawley rats were used (body weight 250-400 gr) in two groups: Group I control (6 rats) with choledoco bile duct ligated; two doses of saline solution 0.9% Intraperitoneal, 0.2 ml/100 gr. were administrated. Group II (Same surgical intervention) received two doses of acetaminophen (intraperitoneal) solution (400 mg/Kg). This group was divided in two (6 rats each), one of this was sacrificed at 48 h. and the other one at 120 h. after acetaminophen injection. Total, direct and indirect bilirubin, alkaline phosphatase, ALT and AST transaminases, hematology study, liver weight, histological studies of liver and kidney were performed in all rats. High incidence of liver necrosis ans significative transaminases increases were found in group II. Our results were discussed taking account that recent biliary tract obstruction increase acetaminophen toxicity, at a half doses reported in other studies. It is possible that mixed oxidation system activity of cytochrome P-450 was increased in our research.
 ...
PMID:[Effects of cholestasis on hepatotoxicity of acetaminophen in rats]. 856 72

Increasing evidence regarding free radical-generating agents and inflammatory processes suggests that accumulation of reactive oxygen species can cause hepatotoxicity. A short-chain analog of lipid hydroperoxide, t-butyl hydroperoxide (t-BHP), can be metabolized to free radical intermediates by cytochrome P-450 in hepatocytes, which in turn can initiate lipid peroxidation, affect cell integrity and result in cell injury. In this study, we used t-BHP to induce hepatotoxicity in vitro and in vivo and determined the antioxidative bioactivity of esculetin, a coumarin compound. Our investigations showed that pretreatment with esculetin (5-20 microg/ml) significantly decreased the leakage of lactate dehydrogenase (LDH) and alanine transaminase (ALT), and also decreased the formation of malondialdehyde (MDA) in primary cultured rat hepatocytes induced by a 30-min treatment with t-BHP. An in vivo study in rats showed that pretreatment with esculetin (i.p.) at concentrations of 0.5 and 5 mg/kg for 5 days before a single i.p. dose of t-BHP (0.1 mmol/kg) significantly lowered the serum levels of the hepatic enzyme markers (ALT and AST) and reduced oxidative stress in the liver. Histopathological evaluation of the rat livers revealed that esculetin reduced the incidence of liver lesions induced by t-BHP, including hepatocyte swelling, leukocyte infiltration, and necrosis. Based on the results described above, we speculate that esculetin may play a chemopreventive role via reducing oxidative stress in living systems.
 ...
PMID:Inhibitory effect of esculetin on oxidative damage induced by t-butyl hydroperoxide in rat liver. 1109 84

Cytotoxicity and apoptosis are common problems in the isolation and storage of human hepatocytes. In vitro environments of hepatocytes during cell infusion may be critical to reducing cellular damage and enhancing cell viability. We examined the effects of donor liver histology (40-50% steatosis vs. normal), incubation time, temperature, and three solutions for infusion on banked primary human hepatocytes, by studying: trypan blue exclusion, AST release, LDH release, MTT assay, detection of DNA ladder, and a hepatocyte proliferation assay. In addition, the microstructure functions of the endoplasmic reticulum and mitochondria of the intact hepatocytes were determined by measuring correlates of UGT 1A1 and cytochrome P-450 3A (CYP3A4) activity. In general, hepatocyte viability decreased significantly within 60 min after thawing. Cells suspended in 5% dextrose lactated Ringers solution (D5LR) maintained greater cell viability. Hepatocytes from normal liver donors showed less AST and LDH enzyme leak in comparison with cells from fatty liver donors. Mild hypothermic temperature (32 degrees C) inhibited cellular damage that otherwise significantly increased at 60 min. Hepatocytes did not proliferate until 12 h from thaw, regardless of supernatant or conditions of suspension. CYP3A4 activity and a marker for UGT 1A1 activity in hepatocytes from normal donor livers were higher than those from steatotic donor livers. These findings suggest that hepatocytes suspended for infusion after isolation from normal liver donors have normal biological functions and less cellular damage/necrosis in contrast with those isolated from fatty liver donors. These damages are inhibited significantly by maintaining hepatocytes at a mild hypothermic temperature (32 degrees C). D5LR alone maintained the best cell viability for up to 60 min. Media of D5LR + adenosine and HMM were able to partially inhibit hepatocyte apoptosis in hepatocytes from steatotic livers.
 ...
PMID:Optimization of conditions for clinical human hepatocyte infusion. 1564 38

Acetaminophen-induced toxicity has been attributed to cytochrome P-450-generated metabolites, which covalently modify target proteins. However, the mechanism of liver injury pathogenesis needs to be further elucidated. Platelet-activating factor (PAF) is one of the mediators involved in inflammatory tissue alterations associated with acute liver failure. In this study, alterations in blood PAF levels and the serum activity of PAF-acetylhydrolase (PAF-AH) were investigated over the time course of liver injury and regeneration induced by acetaminophen treatment in rats. The administration of a toxic dose of acetaminophen (3.5 g/kg) in rats caused acute hepatic injury, as evident by alterations of biochemical (serum enzymes: ALT, AST and ALP) and liver histopathological (degree of inflammation and apoptosis) indices between 20 and 40 h post-treatment. The hepatic damage was followed by liver regeneration, made evident by three independent indices ([3H]thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index), presenting a peak at 72 h. The PAF levels were elevated at 24 and 28 h, presenting a remarkable peak at 32 h post-treatment. PAF-AH activity presented different kinetics to that of PAF. The enzyme activity was relatively low at all time points examined before the rise in PAF activity, peaking later, at 72, 84 and 96 h. Our data demonstrate that PAF is involved in the pathogenesis of acute liver failure and in augmented compensatory liver tissue repair post-acetaminophen treatment. However, the putative role of PAF during liver toxicity and regeneration remains to be established.
 ...
PMID:Platelet-activating factor (PAF) involvement in acetaminophen-induced liver toxicity and regeneration. 1599 53

Aims: This study was designed to determine if vitamin D receptor (VDR), carrier globulin/binding protein (GC), and cytochrome P-450 family 2, subfamily R, polypeptide 1 (CYP2R1) gene polymorphisms are risk factors in the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients from Northeast India. Materials and Methods: A total of 351 HCV-infected patients were enrolled of which 167 were diagnosed with chronic hepatitis C (CHC), 124 with liver cirrhosis (LC), and 60 with HCC together with 102 age- and sex-matched healthy controls. VDR (BsmI, ApaI, and TaqI), GC (rs4588, rs7051), and CYP2R1 (rs10741657) gene polymorphisms were genotyped for all subjects. Statistical data were analyzed using SPSS ver. 22.0. Results: The frequency of the ApaI CC genotype, ApaI C allele, and bAt haplotype of the VDR gene was significantly higher in HCC and LC patients than controls. After adjusting for other covariates (age, gender, platelet count, AST, ALT, serum albumin, and viral load) logistic regression analysis showed that the ApaI CC genotype and bAt haplotype were independent predictors of HCC development. No significant associations was found for the GC and CYP2R1 polymorphisms examined with the occurrence of HCC. Conclusions: The presence of the VDR ApaI CC genotype and bAt haplotype appear to be important indicators in the development of HCC among HCV-infected patients. Larger studies are needed to further clarify and establish this potential causal relationship.
 ...
PMID:Role of VDR, GC, and CYP2R1 Polymorphisms in the Development of Hepatocellular Carcinoma in Hepatitis C Virus-Infected Patients. 3094 19