Effect of cypermethrin on induction and inhibition of hepatic cytochrome P450 isoforms CYP1A, CYP2B, CYP2E1 and CYP3A4 in Clarias batrachus (Linnaeus)

Abstract

Cypermethrin, a synthetic pyrethroid, has dramatically increased as a substitute for organochlorine and organophosphate insecticides because of their low environmental persistence. However, its high toxicity to aquatic species like fish is manyfold compared to mammals and birds and is a subject of concern. Cytochrome P450 (CYP 450) is a diverse family of Phase I enzymes that catalyse the metabolism of xenobiotics that enter the body and play a vital role in detoxification as the first line of defense against xenobiotics. The current study explores the ability of several hepatic CYP 450 isoforms to metabolise cypermethrin in fish, Clarias batrachus administered with 1/3 sub-lethal concentration (1.9 μg/L) of LC50 value calculated in the laboratory for a period of 5, 10 and 15 days. The liver somatic index (LSI), total microsomal protein content, and total CYP 450 content were also analysed. All treated groups had a slight increase in LSI, while all treated groups had considerably higher levels of total microsomal protein and total CYP 450 content (p<0.05; p<0.01). All three treatment groups experienced a significant (p<0.01) increase in CYP1A-mediated EROD activity. When compared to the control, the CYP2E1-mediated aniline hydroxylase activity (p<0.05) and the CYP2B-mediated N, N-dimethylaniline demethylase activity (p<0.05; p<0.01) significantly increased in the 10 and 15-day treatment groups, respectively. All of the treated groups showed a significant (p<0.05; p<0.01) decrease in CYP3A4-mediated erythromycin demethylase activity when compared to the control. According to these findings, CYP1A was the most sensitive isoform that was investigated and has potential use as a biomarker compared to other isoforms. Cypermethrins severe toxicity to fish has also been linked to its suppression of CYP3A4, a prominent isoform responsible for xenobiotic metabolism in birds and mammals. Since CYP 450 isoforms are crucial regulatory enzymes, changes brought on by pyrethroids may significantly affect the physiological fitness of aquatic organisms.