The effect of hypoxia on hepatic cytochromes and heme turnover in rats in vivo.
We evaluated the effect of hypoxia (7% v/v) on hepatic heme turnover in vivo and microsomal heme protein content in male Sprague-Dawley rats. Hepatic heme protein turnover, measured as 14CO-production during continuous infusion of 5-14C-aminolevulinic acid, a precursor of nonerythrogenic heme, was decreased 60% during hypoxia and returned to control levels promptly after reoxygenation. Hepatic cytochrome P-450 content was decreased in hypoxic and 24-h reoxygenated animals. We conclude that normobaric hypoxia decreases hepatic cytochrome P-450 which could contribute to decreased drug metabolism in hypoxia. This decrease is probably due to heme oxygenase-independent breakdown of hepatic heme.
Jordi-Racine
A L
AL
Department of Clinical Pharmacology, University of Bern, Switzerland.
Alvarez
E
E
Reichen
J
J
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains
D003580:Cytochromes; D002245:Carbon Dioxide; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D006419:Heme Oxygenase (Decyclizing); D003576:Electron Transport Complex IV