Influence of single and concurrent clofibrate and phenobarbital administration on cytochrome P450-dependent mixed function oxidase activities and peroxisome proliferation in male rat liver.
The influence of both single and concurrent administration of phenobarbital and clofibrate on hepatomegaly, cytochrome P450-dependent mixed function oxidase activities, and peroxisome proliferation in male rat liver have been studied. Both xenobiotics separately increase the liver: body weight ratio and their combined administration results in greater hepatomegaly than either compound alone. Both compounds induce NADPH-cytochrome c(P450) reductase activity and laurate omega- and omega-1-hydroxylase activities, but only phenobarbital induces pentoxyresorufin-O-dealkylase. None of the drug treatments induced microsomal cytochrome b5. Phenobarbital did not cause peroxisome proliferation and inhibited the corresponding clofibrate-dependent proliferation. Taken collectively, our studies have demonstrated that concomitant treatment with phenobarbital and clofibrate are largely permissive with respect to the hepatic mixed function oxidase system but have opposing effects on the phenomenon of peroxisome proliferation in the same tissue.
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University of Surrey, School of Biological Sciences, Guildford, England, UK.
Shackleton
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Goldfarb
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Gibson
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Sharma
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Howes
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D000818:Animals; D015153:Blotting, Western; D002994:Clofibrate / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D002994:Clofibrate; D010634:Phenobarbital