Effects of microsomal induction and inhibition on styrene-induced acute hepatotoxicity in rats.
Administration of a single high dose of styrene (878 mg/kg ip in corn oil) to young male rats produced significant elevations in the activities of serum transaminases: 230, 209, and 71% 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. These results demonstrated that styrene could produce acute hepatic injury in young rats. Urinary nonprotein sulfhydryl contents and mandelic, phenylglyoxylic, and hippuric acids were all 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, for example, 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. In addition, such pretreatments further increased the nonprotein sulfhydryl contents at 2 and 6 h after styrene injection. Pretreatment of rats with the microsomal enzyme inhibitor SKF 525-A failed to prevent the hepatotoxicity induced by styrene and did not modify the overall urinary excretion profiles of styrene metabolites. This study suggests that the mechanism of the activation/deactivation process leading to the metabolism and hepatotoxicity of styrene is complex and that alternative pathways not dependent on cytochrome P-450 might also be involved.
D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D001711:Biotransformation; D004790:Enzyme Induction; D008099:Liver / Q000187:drug effects*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology*; D011335:Proadifen / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000032:analysis; D013343:Styrenes / Q000378:metabolism / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000032:analysis
D012709:Serum Albumin; D013343:Styrenes; D013438:Sulfhydryl Compounds; D008748:Methylcholanthrene; D011335:Proadifen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010634:Phenobarbital