Effect of Carrageenan-Induced Inflammation on the Induction of Hepatic Microsomal Enzymes by Phenobarbital and Benzo [α] pyrene in Male Rats

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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, 80mg/kg, i.p., 24h prior to death), or benzo [α] pyrene (BP, 40mg/kg, i, p., 24h 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×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.
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