title: The effect of cianidanol on rat hepatic monooxygenase activities.
abstract: The antinecrotic hepatoprotective agent cianidanol ((+)-catechin, (+)-cyanidan-3-ol, Catergen) has been tested for its ability to interfere with rat liver monooxygenase activities. In vitro, the drug was found to inhibit biphenyl 4-hydroxylation in microsomes from uninduced rats, and aminopyrine N-demethylase in microsomes from uninduced and PB-treated rats, with IC50 just below 1 x 10(-3) mol/l. The compound is less active in inhibiting biphenyl 2- and 4-hydroxylation and ethoxyresorufin 0-deethylation in microsomes from 3-methylcholanthrene-treated rats. Kinetically, cianidanol behaves as a non-competitive inhibitor in all reactions investigated. It binds to oxidized cytochrome P-450 as a ligand (modified type II binding spectrum). The drug does not decrease levels of cytochrome P-450, but rather protects the enzyme from lipoperoxidation-mediated destruction. In vivo, a single dose of cianidanol does not inhibit [14C]-aminopyrine metabolism. Only after 5 days administration a weak but statistically significant inhibitory effect is detected. The mechanism of action of cianidanol is discussed.
mesh_terms: D000632:Aminopyrine / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism; D001944:Breath Tests; D002392:Catechin / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats
chemical_list: D001578:Benzopyrans; D001713:Biphenyl Compounds; D000632:Aminopyrine; D002392:Catechin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D000633:Aminopyrine N-Demethylase