Effects of cypermethrin on monoamine transporters, xenobiotic metabolizing enzymes and lipid peroxidation in the rat nigrostriatal system

Abstract

Long-term exposure to cypermethrin induces the nigrostriatal dopaminergic neurodegeneration in adult rats and its pre-exposure in the critical periods of brain development enhances the susceptibility during adulthood. Monoamine transporters, xenobiotic metabolizing enzymes and oxidative stress play critical roles in the nigrostriatal dopaminergic neurodegeneration. The study was undertaken to investigate the effects of cypermethrin on DAT, VMAT 2, CYP2E1, GST Ya, GST Yc and GSTA4-4 expressions, CYP2E1 and GST activities and lipid peroxidation in the nigrostriatal system of adult rats with/without post-natal exposure to cypermethrin. Cypermethrin reduced VMAT 2 and increased CYP2E1 expressions without causing significant change in DAT. Although GSTA4-4 mRNA expression and lipid peroxidation were increased, no significant changes were observed in GST Ya and GST Yc expressions and total GST activity. The results obtained demonstrate that long-term exposure to cypermethrin modulates VMAT 2, CYP2E1, GSTA4-4 expressions and lipid peroxidation, which could contribute to the nigrostriatal dopaminergic neurodegeneration.

Keywords::

• Cypermethrin
• dopamine transporter
• vesicular monoamine transporter 2
• oxidative stress
• lipid peroxidation
• Parkinson's disease

Declaration of interest: Authors thank the Council of Scientific and Industrial Research (CSIR), New Delhi, for providing a research fellowships to Manindra Nath Tiwari, Anand Kumar Singh, Israr Ahmad and Ghanshyam Upadhyay. The IITR communication number of this article is 2857. The study was supported financially by the Council of Scientific and Industrial Research (CSIR), New Delhi through supra-institutional project ‘Investigative Toxicology: New Paradigms (SIP-08)’.

This paper was first published online on Early Online on 25 August 2010.