Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic ischemia induced in vivo by ligation of the left hepatic lobe of rats for up to 2 hr had no effect on cytochrome P-450, cytochrome c reductase, or lobe histology; however, cytochrome b5 increased with ischemia duration. Ethylmorphine demethylation decreased 35% after 2 hr of ischemia. Reperfusion of tissue previously made ischemic for up to 2 hr was associated with appreciable necrosis as well as decreases in cytochrome P-450, cytochrome b5, cytochrome c reductase, and ethylmorphine demethylation. Serum alanine transaminase and aspartate transaminase concentrations were increased by reperfusion of previously ischemic tissue. Reperfusion of the previously ischemic lobe for 18 hr was associated with a greater loss of cytochromes P-450 and b5, cytochrome c reductase, and ethylmorphine demethylation than reperfusion for 1 hr. The total decrease in cytochrome P-450 and b5 content was equal to the decrease in total microsomal heme content, although cytochrome P-450 decreased more than cytochrome b5. Ethoxyresorufin deethylation by hepatic microsomes from 3-methylcholanthrene-treated rats was decreased by ischemia-reperfusion; however, pentoxyresorufin dealkylation by hepatic microsomes from phenobarbital-treated rats was not, suggesting specific cytochrome P-450 isozyme loss. In vitro NADPH-dependent lipid peroxidation in hepatic microsomes from control and phenobarbital- and 3-methylcholanthrene-treated rats resulted in a selective decrease of ethoxyresorufin but not pentoxyresorufin dealkylation, similar to that observed in livers subjected to ischemia-reperfusion in vivo. These data suggest that cytochrome P-450, ethylmorphine demethylation, and ethoxyresorufin deethylation are more susceptible to ischemia-reperfusion injury than cytochrome b5 or pentoxyresorufin dealkylation.
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PMID:Effects of hepatic ischemia-reperfusion injury on the hepatic mixed function oxidase system in rats. 225 Jun 63

Ketoconazole (KC), a broad spectrum antifungal drug, has been recognized recently as a cause of hepatic injury. The mechanism of the adverse reaction remains unclear: a metabolic idiosincrasy has been suggested. However as a substituted imidazole, KC might be expected to interfere with the hepatic microsomal mixed function oxidases. Ethylmorphine N-demethylase (E-DM) and aniline hydroxylase (A-OH) activities were determined in rat liver microsomes in the presence of increasing amounts of KC. Both were inhibited in an exponential fashion. The E-DM inhibition was almost complete at concentrations greater than 250 microM and was of the mixed type. A much weaker effect was observed for A-OH. A significant inhibition of E-DM was also observed when KC was administered in vivo to rats either orally for 7 days at the dose of 100 mg/kg/day (P less than 0.02) or intraperitoneally for 4 days at the dose of 50 or 100 mg/kg day (P less than 0.01 or P less than 0.001 respectively). A-OH activity was significantly reduced (P less than 0.01) only after ip administration of 100 mg/kg/day of the drug for 4 days. Neither the amount of cytochrome P-450 nor NADPH cytochrome c reductase activity were affected at the doses considered. These data show that KC interferes with hepatic oxidative drug metabolism and suggest that this mechanism might be involved in the unwanted side effects of therapy with KC.
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PMID:In vivo and in vitro inhibition of hepatic microsomal drug metabolism by ketoconazole. 393 32

Studies were carried out to investigate the mechanism(s) responsible for the changes in adrenal microsomal mixed function oxidase activity which occur with aging (30-200 days) in guinea pigs. With aging, the rate os metabolism of xenobiotics [ethylmorphine and benzo(a)pyrene] by adrenal microsomes increased 3- to 5-fold. Steroid 17 alpha- and 21-hydroxylations, when expressed per mg protein, were similar in immature (30 days old) and mature (200 days old) animals. Adrenal microsomal NADPH- and NADH-cytochrome c reductase activities and cytochrome b5 concentrations increased wih aging, but cytochrome P-450 concentrations were not significantly different in young and old guinea pigs. Maximal type I difference spectra produced by steroids were the same in adrenal microsomes from 30- and 200-day-old guinea pigs, but the ethylmorphine-induced spectrum was far greater in the older animals. Progesterone enhanced NADPH-cytochrome P-450 reductase activity to about the same extent in adrenal microsomes from 30- and 200-day-old guinea pigs. Ethylmorphine had no effect on the rate of reduction of cytochrome P-450 in adrenals from young animals but produced a 4-fold increase in activity in adrenals from older animals. The results demonstrate selective changes in adrenal xenobiotic metabolism with aging and suggest that changes in the composition and/or reactivity of adrenal cytochromes P-450 are responsible for the effects of aging.
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PMID:Changes in adrenal microsomal cytochrome(s) P-450 with aging in the guinea pig. 677 26