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)

This study was undertaken to determine the effects of two H2-receptor antagonists, cimetidine and ranitidine, on halothane metabolism and hepatotoxicity in the hypoxic Fisher 344 rat model for halothane hepatitis. In this model, liver injury is caused by toxic intermediates formed during metabolism of halothane by a reductive pathway. Administration of cimetidine (120 mg/kg ip) 20 min prior to anesthesia led to inhibition of the reductive pathway, as assessed by measurement of the exhaled metabolites, 2-chloro-1,1,1-trifluoroethane and 2-chloro-1,1-difluoroethylene, during anesthesia, and urinary fluoride excretion in the 22-hr postanesthesia period. Oxidative metabolism of halothane, assessed by serum bromide concentrations 22 hr postanesthesia, was unaffected. Cimetidine administration provided partial protection against the hepatotoxic effect of halothane, as indicated by serum alanine aminotransferase activities 22 hr postanesthesia. When ranitidine HCl (120 mg/kg ip) was administered prior to anesthesia, reductive metabolism of halothane was unaffected, but the oxidative pathway was slightly inhibited. Ranitidine did not provide protection against halothane-induced liver injury. These results provide additional evidence that halothane hepatotoxicity in the hypoxic rat model is due to toxic intermediates formed during the reductive metabolism of halothane.
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PMID:Effects of cimetidine and ranitidine on halothane metabolism and hepatotoxicity in an animal model. 614

H2 receptor antagonist-hepatotoxicant interactions were evaluated in male Fischer-344 rats. The H2 receptor antagonists, cimetidine, ranitidine, oxmetidine, and 2-[2-(2-dimethyl-aminomethyl-5-furanylmethyl-thio)-ethylamino]-5-( 6-methyl- 3-picolyl)-4-pyrimidine trihydrohydrochloride (SK&F 93479) were administered (p.o.) at a dose of 0.143 mMoles/kg 30 minutes prior to hepatotoxicant treatment. Submaximal hepatotoxic doses (p.o.) of carbon tetrachloride (795 mg/kg), bromobenzene (748 mg/kg), chloroform (1,190 mg/kg), allyl alcohol (60 mg/kg), galactosamine (200 mg/kg, i.p.), and acetaminophen (1000 mg/kg) were employed. Hepatotoxicity was evaluated by determining serum alanine aminotransferase activity (ALT). Pretreatment with the H2 receptor antagonists did not significantly alter carbon tetrachloride or allyl alcohol hepatotoxicity. Bromobenzene and chloroform toxicities were unaffected by cimetidine, ranitidine, and oxmetidine pretreatment but were potentiated by SK&F 93479. Cimetidine and ranitidine decreased galactosamine mediated hepatotoxicity. Acetaminophen hepatotoxicity was markedly potentiated by ranitidine pretreatment but was unaltered by the other three H2 receptor antagonists. The mechanisms of hepatotoxicity potentiation or protection have not been determined, however, the lack of consistent H2 receptor antagonists effects indicates that it is unlikely that alterations in G.I. pH account for the effects observed. H2 receptor antagonist mediated changes in hepatotoxicant metabolism provide a more plausible mechanism of action, particularly in the cases of SK&F 93479 potentiation of bromobenzene and chloroform and ranitidine potentiation of acetaminophen hepatotoxicity.
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PMID:Effects of H2 receptor antagonists on the hepatotoxicity of various chemicals. 614 1

Liver injury produced by CCl4 depends on its metabolism by the liver cytochrome P450 enzyme system to a highly reactive intermediate (CCl3.). Cimetidine impairs cytochrome P450 and stimulates regenerative processes acting on DNA synthesis. This work was performed to investigate whether cimetidine may prevent CCl4-induced liver cirrhosis. Male Wistar rats were used: animals in group 1 received CCl4 (0.04 g per 100 g, i.p.) three times a week for 8 weeks; group 2 was treated with CCl4 plus cimetidine (120 mg kg-1, p.o.) three times a week for 8 weeks; group 3 received CCl4 for 8 weeks and then cimetidine for 4 weeks. Alkaline phosphatase, gamma-glutamyl transpeptidase (gamma-GTP) and alanine aminotransferase (ALT) activities, as well as protein and bilirubin, were measured in serum; collagen and lipoperoxidation were quantified in liver. Intoxication with CCl4 increased (P < 0.05) serum activities of alkaline phosphatase, gamma-GTP and ALT, and bilirubin concentration; liver collagen and lipoperoxidation were also increased. Cimetidine treatment prevented or reverted the increases in the three enzyme activities and in bilirubin content and the fall in proteins. It is worth noting that cimetidine co-treatment completely prevented both the increase in collagen content and the lipid peroxidation. The protective effect of cimetidine can be attributed to a reduction in cytochrome P450. However, it could also stimulate regenerative processes.
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PMID:Cimetidine prevents and partially reverses CCl4-induced liver cirrhosis. 791 3

Abstract:Background andObjectives: Immunosuppressed individuals are at particularly increased risk for human papilloma virus-related infections. The primary objective of our study is to determine if there are any adverse effects associated with high-dose cimetidine treatment. A secondary objective is to report our experience with cimetidine in the treatment of cutaneous warts in pediatric heart transplant recipients. Methods and Results: This was a retrospective observational study. A total of 8 pediatric heart transplant recipients diagnosed with multiple recalcitrant warts were the subject of the study. All patients were treated with cimetidine (30-40 mg/kg/day) in two divided doses for 3 to 6 month durations. All patients had complete resolution of their lesions except 1 patient who had no clinical improvement. Of these 8 patients, one had recurrence of warts at one year follow-up, which resolved with restarting cimetidine therapy. One patient who had only 3 months of cimetidine therapy had immediate relapse after cimetidine was stopped. None of them had significant change in their tacrolimus trough, serum creatinine, and alanine transaminase levels. No adverse events were reported except one patient experienced mild gynecomastia. Conclusion: Cimetidine can be a safe and alternative treatment option for multiple warts in pediatric heart transplant recipients.
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PMID:Cimetidine: A Safe Treatment Option for Cutaneous Warts in Pediatric Heart Transplant Recipients. 2964 99