Action on mitochondria and toxicity of metabolites of tri- n-butyltin derivatives

Abstract

Tri- n-butyltin derivatives are metabolized by a cytochrome P450-dependent rat liver microsomal monooxygenase system and by mice to yield carbon-hydroxylated metabolites, i.e. the α-, β-, γ- and δ-hydroxybutyl-dibutyltin derivatives, as well as the corresponding γ-ketone. The latter three metabolites are sufficiently stable at physiological pH for comparisons with tributyltin chloride with regard to their action on mitochondrial functions and intraperitoneal toxicity to mice. The δ-hydroxy compound differs most greatly from the other metabolites in potency for altering mitochondrial functions possibly because of its greater polarity or its lower propensity for intramolecular coordination of the introduced oxygen with the tin atom. The γ-hydroxy, δ-hydroxy and γ-keto compounds are less toxic to mice than tributyltin derivatives and do not increase the water content of the brain under conditions where triethyltin bromide does.