Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary cultures of adult rat hepatocytes were established using two different isolation procedures: a two-step collagenase perfusion and a method using ethylenediaminetetraacetate (EDTA) as the dissociating agent. Both techniques provided good yields of hepatocytes with comparable viability. The evolution of hepato-specific protein levels and several drug-metabolizing enzyme activities were followed for 8 days in cultured hepatocytes obtained by both methods. EDTA-isolated hepatocytes maintained a low gamma glutamyltransferase (GGT) activity, whereas collagenase-treated cells acquired a high GGT level. Transferrin secretion and tyrosine aminotransferase (TAT), alanine aminotransferase (ALT), and microsomal epoxide hydrolase (mEH) activities were stable in both EDTA- and collagenase-isolated hepatocytes, whereas albumin secretion, aspartate amino transferase (AST) activity, total cytochromes P-450 content, IA1 and IIB1 P-450 isoenzymes, NADPH-cytochrome P-450 reductase (EC 1.6.2.4) levels, and bilirubin glucuronidation decreased faster in collagenase-treated cells. The most important difference observed was the maintainance of the mixed-function oxidase system in EDTA-isolated hepatocytes. These results emphasize the critical role of isolation technique in stabilization of differentiated hepatocytes in primary culture.
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PMID:Influence of the isolation method on the stability of differentiated phenotype in cultured rat hepatocytes. 185 20

Exposure to chlordecone (CD, Kepone) is known to increase the hepatotoxicity of chloroform (CHCl3) in rats. A time-course analysis was conducted relating several indices of biotransformation capacity with the ability of CD to potentiate CHCl3-induced hepatotoxicity. Male Sprague-Dawley rats were given a single administration of corn oil alone or CD (50 mg/kg, po) dissolved in corn oil. At 2, 4, 8, 16, 20, 24, or 32 days posttreatment, groups of rats were killed and their livers were analyzed for (i) cytochrome P-450, NADPH-dependent cytochrome c reductase, cytochrome b5 and glutathione content or (ii) in vitro irreversible binding of 14CHCl3-derived radiolabel to microsomal protein. Similarly treated rats were challenged (2-32 days posttreatment) with CHCl3 (0.5 mL/kg po); 24 h later, liver damage was assessed by plasma alanine aminotransferase (ALT), plasma ornithine carbamyl transferase (OCT), plasma bilirubin, and hepatic glucose-6-phosphatase. CD potentiation was maximal 2 days posttreatment; and enhanced susceptibility to CHCl3 persisted up to 20-24 days post-CD treatment. In a parallel study animals treated with chlordecone were killed 8, 16, 20, 24, or 32 days later. Blood, kidney, liver, and adipose tissue samples were taken and analyzed for chlordecone content. The results suggest that a general temporal correlation exists between biotransformation rate (microsomal 14C binding), chlordecone content, and the severity of liver injury; the other parameters monitored do not appear to relate directly to the potentiation.
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PMID:Temporal relationships between biotransformation, detoxication, and chlordecone potentiation of chloroform-induced hepatotoxicity. 242 14

The effects of allyl alcohol, galactosamine, bromobenzene, and corn oil administration were evaluated in male Fischer 344 rats at 4 to 5, 14 to 15, and 24 to 25 months of age to determine if susceptibility to hepatotoxic injury is modified as a consequence of aging. Parameters measured were (1) severity of hepatocellular necrosis as judged by light microscopy of liver sections, (2) activity of alanine aminotransferase and aspartate aminotransferase in serum, and (3) hepatic microsomal cytochrome P-450 content and NADPH-cytochrome P-450 reductase activity. Allyl alcohol toxicity was more severe in middle-aged and old rats than in young-adult rats. In contrast, galactosamine and bromobenzene toxicities were slightly decreased or unchanged in old rats. The results demonstrate that aging has effects on some types of chemically induced hepatotoxicity.
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PMID:Influence of aging on the susceptibility of rats to hepatotoxic injury. 671 May 24

The present study reports on the effects of horminone on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, on hepatic cytochrome P450 (P450) and cytochrome b5 (cyt b5) contents and on the activities of NADPH-cytochrome P450 reductase (NR), mixed function mono-oxygenases (MFO), glutathione-S-transferase (GST) and glutathione reductase (GR) of Wistar male rat. Horminone is a diterpenoid quinone (7,12-dihydroxyabiet-8,12-diene-11,14-dione) present in several species of the Labiatae family and used as medicinal plants in folk medicine. In this study, horminone was administered by the intraperitoneal route (i.p.) at a concentration of 1 or 10 mg/kg to each group of six mice, using water as a vehicle. On the one hand, results showed that horminone increased serum ALT and AST levels and cyt b5 content and induced the activities of ethylmorphine N-demethylase (EMD). On the other hand, horminone decreased P450 content and inhibited the activities of 7-ethoxyresorufin O-deethylase (ERD), 7-ethoxycoumarin O-deethylase (ECD), aniline 4-hydroxylase (AH) and NR. Based on these results, the possibility of toxic effects occurring after administration of plant extracts containing horminone must be considered.
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PMID:Effects of horminone on liver mixed function mono-oxygenases and glutathione enzyme activities of Wistar rat. 932 1

Enzyme activity modulation by cadmium in the liver of the teleost fish Sparus aurata was investigated in vivo following 3 and 6 days of CdCl2 administration (2.5 mg/kg body wt). The specific activities of the mitochondrial enzymes NAD-isocitrate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase were stimulated by approximately 20% after 3 days administration and were further increased (by about 40%) after 6 days treatment. In comparison with these enzymes, the activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) in mitochondria were less stimulated after the two indicated intervals of treatment. Cadmium significantly reduced the activities of liver cytoplasmic GOT and GPT while a simultaneous increase occurred in the serum activities of these same enzymes. The activity of liver NADPH-cytochrome P450 reductase was stimulated by 25 and 40% after 3 and 6 days cadmium intoxication, respectively. Lastly, the antioxidant enzymes glutathione peroxidase and glutathione reductase in liver and catalase in both liver and blood were strongly reduced after 3 and 6 days cadmium administration. These data suggest that cadmium in fish hepatocytes alters cell membrane structure and concomitantly induces some perturbation in the integrity of the mitochondrial membrane.
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PMID:Changes in liver enzyme activity in the teleost Sparus aurata in response to cadmium intoxication. 1033 Mar 29

1. The aim of this study was to investigate the effect of Trolox on hepatic microsomal cytochrome P450 (CYP) activity and gene expression during ischemia and reperfusion (I/R). 2. Rats were subjected to 60 min of hepatic ischemia, and 5 h (acute phase) and 24 h (subacute phase) of reperfusion. Rats were treated intravenously with Trolox (2.5 mg kg(-1)) or vehicle, 5 min before reperfusion. 3. The serum alanine aminotransferase level and lipid peroxidation were increased as a result of I/R. These increases were attenuated by Trolox. Reduced glutathione concentration decreased in I/R group, and this decrease was inhibited by Trolox. 4. Both total hepatic CYP content and NADPH-cytochrome P450 reductase activity decreased after I/R, which were restored by Trolox. 5. CYP1A1 activity and its protein level decreased 24 h after reperfusion; decreases which were prevented by Trolox. Both the activity and mRNA expression of CYP1A2 decreased 24 h after reperfusion. The decrease in CYP1A2 mRNA was prevented by Trolox. CYP2B1 activity and mRNA expression decreased 5 h after reperfusion. The decrease in CYP2B1 activity was prevented by Trolox. In contrast, the CYP2E1 activity and its protein level increased 5 h after reperfusion and this increase was prevented by Trolox. 6. The expression of TNF-alpha and iNOS mRNAs increased after I/R. Trolox inhibited increase in iNOS mRNA expression. 7. Trolox ameliorates hepatic drug-metabolizing dysfunction, as indicated by abnormalities in CYP isoforms during I/R, and this protection is likely due to the scavenging of reactive oxygen species.
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PMID:Effects of Trolox on the activity and gene expression of cytochrome P450 in hepatic ischemia/reperfusion. 1505 25