Actions of orally administered organotin compounds on heme metabolism and cytochrome P-450 content and function in intestinal epithelium

Abstract

The gastrointestinal tract is a major route by which humans are exposed to environmental chemicals. We have examined in these studies the effects of oral administration of organotin compounds in the small intestinal epithelium, an organ which exhibits highly active drug and other chemical metabolism. A series of n-butyltin compounds was administered by gavage to male Sprague-Dawley rats (225–275 g) in single doses up to 250 μmol/kg body weight. Bis(tri- n-butyltin)oxide (TBTO) produced dose- and time-dependent decreases in the content and functional activity of intestinal cytochrome P-450, together with an elevation (3-fold) in the activity of musomal heme oxygenase. The effects of di- n-butyltin dichloride on heme oxygenase and cytochrome P-450 were pronounced in the small intestine and extended to the liver and kidneys within 24 hr after oral exposure, whereas TBTO did not affect the liver until much later (6 days), when cytochrome P-450 content was reduced markedly (30%). Furthermore, the effects produced by tetra- n-butyltin on cytochrome P-450 at 24 hr were localized in the intestinal epithelium. These studies indicate important pharmacological effects of organotin compounds in the gut, and raise the possibility that concurrent oral ingestion of organotins with other environmental pollutants may alter the cytochrome P-450-dependent metabolism of xenobiotics and natural substrates of this monooxygenase system in the small intestine.