Effects of microsomal induction and inhibition on styrene‐induced acute hepatotoxicity in rats

Publisher Website
Google Scholar
Abstract
Administration of a single high dose of styrene (878 mg/kg i.p. in corn oil) to young male rats produced significant elevations in the activities of serum transaminases: 230, 209 and 7 increases in the activity of serum glutamic-oxaloacetic transaminase (SGOT) and 163, 437 and 227% in that of serum glutamic-pyruvic transaminase (SGPT) at 2, 6 and 24 h, respectively, after the dose. Styrene produced acute hepatic injury in young rats. Urinary nonprotein SH contents and mandelic, phenylglyoxylic and hippuric acids increased. Pretreatment of rats with phenobarbital and 3-methylcholanthrene did not further enhance the activities of SGOT and SGPT after styrene but produced changes in other biochemical parameters such as an increase in liver weight, decrease in serum albumin and globulin concentrations, increase in serum alkaline phosphatase activity at 2 and 6 h and increase in urinary urobilinogen concentrations. Pretreatment further increased the nonprotein SH contents at 2 and 6 h after styrene injection. Pretreatment of rats with the microsomal enzyme inhibitor SKF 525-A [proadifen hydrochloride] failed to prevent the hepatotoxicity induced by styrene and did not modify the overall urinary excretion profiles of styrene metabolites. The mechanism of the activation/deactivation process leading to the metabolism and hepatotoxicity of styrene was complex and alternative pathways not dependent on cytochrome P-450 might also be involved.

This publication has 17 references indexed in Scilit: