Abstract |
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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Authors | T D Lindstrom, B R Hanssen, A M Bendele |
Journal | Molecular pharmacology
(Mol Pharmacol)
Vol. 38
Issue 6
Pg. 829-35
(Dec 1990)
ISSN: 0026-895X [Print] United States |
PMID | 2250663
(Publication Type: Journal Article)
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Chemical References |
- Isoenzymes
- Cytochromes b5
- Cytochrome P-450 Enzyme System
- Mixed Function Oxygenases
- NADH Dehydrogenase
- Phenobarbital
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Topics |
- Animals
- Cytochrome P-450 Enzyme System
(analysis)
- Cytochromes b5
(analysis)
- Ischemia
(enzymology)
- Isoenzymes
(analysis)
- Lipid Peroxidation
- Liver
(blood supply, enzymology)
- Male
- Mixed Function Oxygenases
(analysis)
- NADH Dehydrogenase
(analysis)
- Phenobarbital
(pharmacology)
- Rats
- Rats, Inbred Strains
- Reperfusion Injury
(enzymology)
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