Inorganic tin—a new selective inducer of the murine coumarin 7-hydroxylase (CYP2A5)

Abstract

The coumarin 7-hydroxylase of mice (Coh, CYP2A5) is known to be highly selectively inducible by both a set of heavy metals such as cobalt, indium and cerium and a variety of organic nitrogen-containing heteroaromatic compounds such as 3-amino-1,2,4-triazole, pyrazine and pyrazole. The investigations presented reveal that inorganic divalent tin has to be included in the list of selective inducers. Pretreatment of NMRI-mice with 50 mg SnCl₂/kg body weight, daily for 2 days, increases the coumarin hydroxylation 40- and 20-fold in the kidney and liver, respectively. So far, the inducing potency of tin chloride is higher than that of the agents already known. The diagnostic inhibitor metyrapone strongly inhibits the coumarin model reaction. In the kidneys tin generates an almost pure fraction of a cytochrome P450 isozyme catalyzing the metabolism of coumarins, as inhibition experiments reveal.