Prolonged induction of hepatic haem oxygenase and decreases in cytochrome P-450 content by organotin compounds

Abstract

The administration of organotin compounds to rats in single doses causes a significant and prolonged induction of heme oxygenase and a sustained decrease in hemoprotein content in the liver. The extent of induction of hepatic heme oxygenase varied between 3 and 5-fold at 72 h after a single injection of water-insoluble organotins of differing structure. The alterations in heme metabolism produced by tricyclohexyltin hydroxyide were studied in detail. The effects were dose-dependent, with doses as low as 3.75 mg/kg body wt resulting in significant induction of heme oxygenase and a decrease in cytochrome P-450 and cytochrome b5 contents at 72 h in the liver. The effects with time of a single dose of tricyclohexyltin on various parameters of liver heme metabolism were also examined. The organotin produced a substantial and very prolonged induction of heme oxygenase accompanied by a steady decline in cytochrome P-450 content for periods up to 8 days. The long duration of action of these organotins with respect to induction of heme oxygenase and depletion of cellular hemoprotein content provides a highly sensitive metabolic system with which to define further the toxic potential of organometals as well as to study the adaptive responses in liver to long-term perturbations of heme metabolism by foreign chemicals.