Inactivation of adrenal cytochromes P450 by 1-Aminobenzotriazole (cas 1614-12-6)

Add time:07/20/2019    Source:sciencedirect.com

Recent investigations demonstrated that administration of 1-aminobenzotriazole (ABT) to rats caused adrenal gland enlargement. Studies were done to pursue the mechanism(s) involved. Preliminary experiments revealed that the adrenal enlargement caused by ABT was associated with a decline in plasma corticosterone concentrations, suggesting inhibition of adrenal steroidogenesis. Indeed, a single injection of ABT (25 or 50 mg/kg body weight) to rats caused concentration-dependent declines (60–80%) in adrenal mitochondrial and microsomal cytochrome P450 (P450) concentrations. The decreases in adrenal P450 levels exceeded those in hepatic microsomes. Accompanying the declines in adrenal P450 concentrations were decreases in steroid hydroxylase activities. Mitochondrial 11β-hydroxylase and cholesterol side-chain cleavage activities and microsomal 21-hydroxylase activity were diminished markedly (60–90%) by ABT treatment. In contrast, activity of adrenal 3β-hydroxysteroid dehydrogenase-isomerase was not affected by ABT, indicating specificity for P450-dependent reactions. Incubation of adrenal microsomes or mitochondria in vitro with ABT plus an NADPH-generating system had no effect on P450 concentrations or on steroid hydroxylase activities. Similar incubations with hepatic microsomes caused declines in P450 levels and in the rates of P450-mediated xenobiotic metabolism. The results demonstrate that ABT is a potent inhibitor of adrenal steroid hydroxylases in vivo, but the in vitro studies indicate that the mechanism of action differs from that on other P450 isozymes. The absence of inhibitor effects in vitro suggests that an extra-adrenal metabolite of ABT is responsible for the in vivo inactivation of steroidogenic enzymes.

We also recommend Trading Suppliers and Manufacturers of 1-Aminobenzotriazole (cas 1614-12-6). Pls Click Website Link as below: cas 1614-12-6 suppliers

Prev:Inhibition of adrenal cytochromes P450 by 1-Aminobenzotriazole (cas 1614-12-6) in vitro selectivity for xenobiotic metabolism
Next:In Vitro Inhibitory Effect of 1-Aminobenzotriazole (cas 1614-12-6) on Drug Oxidations Catalyzed by Human Cytochrome P450 Enzymes: A Comparison with SKF-525A and Ketoconazole)