Selenium antagonism of cadmium-induced inhibition of hepatic drug metabolism in the male rat |
| |
Authors: | Johnnie L. Early R.Craig Schnell |
| |
Affiliation: | Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907 USA |
| |
Abstract: | Experiments were undertaken to examine the effect of selenium, an essential trace element, on cadmium-induced inhibition of drug metabolism in male, Sprague-Dawley derived rats. Prior administration of sodium selenite (1.6 mg Se/kg, ip) blocked the cadmium-induced (0.84 mg Cd/kg, ip) prolongation of hexobarbital-induced hypnosis and inhibition of hepatic microsomal biotransformation of ethylmorphine or aniline. Selenium also blocked cadmium-induced reduction in microsomal cytochrome P-450 content and the microsomal binding of both ethylmorphine and aniline. However, pretreatment of rats with selenium did not prevent the inhibitory effect of cadmium (10?6 to 10?3m) added in vitro on either ethylmorphine or aniline biotransformation. In addition, the reduction in biotransformation of both substrates following in vivo cadmium administration was not reversed following the in vitro administration of selenium but, in fact, selenium produced further concentration-dependent decreases in drug metabolism. In additional in vitro experiments it was found that the inhibition in drug metabolism induced by in vitro additions of cadmium is not affected by similar additions of selenium when added to the incubation vessel either before or after the cadmium. Thus, for selenium to prevent the cadmium-induced inhibition of hepatic drug metabolism requires in vivo administration of selenium. |
| |
Keywords: | Send correspondence to: Department of Pharmacodynamics and Toxicology College of Pharmacy University of Nebraska Medical Center 42nd and Dewey Avenue Omaha Nebraska 68105. |
本文献已被 ScienceDirect 等数据库收录! |
|