Effect of carrageenan-induced inflammation on the induction of hepatic microsomal enzymes by phenobarbital and benzo[a]pyrene in male rats.
The inhibitory effect of carrageenan-induced inflammation was examined by utilizing rats treated with inducers of this drug metabolizing system. Animals were given sodium phenobarbital (PB, 80 mg/kg, i.p., 24 h prior to death), or benzo[a]pyrene (BP, 40 mg/kg, i.p., 24 h prior to death) as inducers. Some animals were also given carrageenan 24 h prior to death. Non-induced male rats exhibited significant decreases in hepatic 9000 x g supernatant (S-9) cytochrome P-450 and aminopyrine (AM) N-demethylase, benzphetamine (BenzP) N-demethylase and meperidine (MP) N-demethylase activity following carrageenan treatment. Carrageenan also depressed the induction of hepatic S-9 cytochrome P-450 content caused by PB treatment, and suppressed the induction of AM, BenzP, MP, arylhydrocarbon and 7-ethoxycoumarine metabolism by PB treatment. Cytochrome P-450 levels and related biotransformation activity which are elevated by BP treatment were not decreased by the injection of BP and carrageenan simultaneously to male rats. Non-induced, PB-treated and BP-treated female rats did not show inhibited carrageenan-induced reduction in hemoprotein content or inhibition of AM-N-demethylase, BenzP N-demethylase and aniline hydroxylase activities. These results demonstrate the selective nature of the inhibitory effects of carrageenan-induced inflammation upon drug metabolism in the rats.
Ishikawa
M
M
Department of Pharmacology and Toxicology, Tohoku College of Pharmacy, Sendai, Japan.
Sasaki
K
K
Takayanagi
Y
Y
Sasaki
K
K
D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D001711:Biotransformation; D002351:Carrageenan / Q000633:toxicity*; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D003580:Cytochromes; D001564:Benzo(a)pyrene; D002351:Carrageenan; D003577:Cytochrome P-450 Enzyme System; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; D000633:Aminopyrine N-Demethylase; C023853:meperidine N-demethylase; D010634:Phenobarbital