The effect of cianidanol on rat hepatic monooxygenase activities.

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.