title: Influence of selenium on the metabolism of bromobenzene and a possible relationship to its hepatotoxicity.
abstract: When male Sprague-Dawley rats were treated with sodium selenite (1 mg/kg, sc) 24 hr prior to or simultaneously with bromobenzene (2.5 mmol/kg, ip) and sacrificed 48 hr after the bromobenzene dose, increased levels of the activities of serum transaminases (serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) induced in the bromobenzene-treated rats were significantly reduced in the presence of selenium. However, no such reduction in the transaminases activities were observed when rats were either pretreated with selenite for 48 hr or pretreated with 0.1, 0.2, or 0.5 mg/kg of selenite. Although selenium alone had no effect on the hepatic microsomal drug metabolism, simultaneous treatment of selenite (1 mg/kg) with bromobenzene resulted only an increase in the activity of aniline hydroxylase after 48 hr as compared to that in the bromobenzene-treated group. When rats were given 2.5, 10, and 20 ppm of selenite in drinking water daily for 4 weeks prior to an ip injection of 2.5 mmol/kg of bromobenzene and were sacrificed 48 hr after bromobenzene administration, a reduction in the SGOT activities in all the pretreated groups and a reduction of SGPT activity in 20 ppm selenite-treated group were observed when compared with those in the bromobenzene-treated groups. A dose-dependent increase in hepatic GSH concentrations were observed due to such chronic selenium treatment. Treatment with selenite (1 mg/kg) 24 hr prior to bromobenzene injection (2.5 mmol/kg) increased initially both o and p-bromophenols in the rat urine at 0-7.5 hr without affecting urinary thioethers. On the contrary, the ratio of thioethers to p-bromophenol was significantly higher in both 2.5 and 10 ppm selenite-pretreated (4 weeks) rats as well as a significant increase in the ratio of thioethers to total phenolic metabolites in 10 ppm and an increase close to significant in 2.5 ppm selenite-treated rats were observed initially at 0-7.5 hr urine samples. These results indicate that acute selenium pretreatment under certain conditions, favors increased hydroxylation of the intermediate bromobenzene epoxides, whereas higher detoxification of the epoxides involving hepatic glutathione (GSH)/GSH transferases pathway is more favored due to increased biosynthesis of GSH in certain chronic selenium treated rats.
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001969:Bromobenzenes / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D020887:Selenious Acid; D012643:Selenium / Q000494:pharmacology*
chemical_list: D001969:Bromobenzenes; D003577:Cytochrome P-450 Enzyme System; C032036:bromobenzene; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020887:Selenious Acid; D012643:Selenium