Role of antioxidant micronutrients on induction of rat liver and brain cytochrome P450 enzymes by fenvalerate

Abstract

The role of an association of micronutrients: omega 3 fatty acids (ω3) and selenium (Se), on the induction of rat liver and brain cytochrome P450 enzymes by fenvalerate (FEN) was investigated. The animals were housed in groups of 10 rats each and divided randomly into 4 groups. Treatments were carried out day by day for 20 days. The first group served as control (C) and injected orally with corn oil, group 2 was injected with a single dose of FEN (20 mg/kg, orally) for 24 h prior to decapitation, group 3 was administered orally with ω3 (20 mg/kg) and Se (4.10 mg/kg; ω+Se), group 4 was administered orally with FEN following the treatment with ω3 and Se (FEN+ω3 +Se). Treatment period extended for 3 weeks. The content of microsomal protein, drug metabolizing enzymes and thiobarbituric acid reactive substances (TBARS) were determined in liver and brain microsomes after treatment. Pretreatment of rats with repeated doses of ω3 and Se prior to the administration of FEN reduced the hepatic and brain content of cytochrome b5 , P450 and the level of TBARS. The activity of glutathione S-transferase (GST) was significantly induced in rat liver and brain in FEN treated group. Also the activity of NADPH cytochrome c-reductase was significantly decreased in liver microsome; while it increased in brain. Pretreatment of rats with ω3 and Se are more effective in decreasing the activity of amidopyrine N-demethylase in rat liver prior to FEN administration. Oral administration of FEN (20 mg/kg) did not cause mortality and had no significant effect on hepatic and brain microsomal protein. It may be concluded that association of micronutrients may reduce the toxic effects exerted by FEN upon liver and brain through inhibition of cytochrome P450 system.