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

• Published in: Free radical research 2010-12, Vol.44 (12), p.1416-1424
• Main Authors: Tiwari, Manindra Nath, Singh, Anand Kumar, Ahmad, Israr, Upadhyay, Ghanshyam, Singh, Dhirendra, Patel, Devendra Kumar, Singh, Chetna, Prakash, Om, Singh, Mahendra Pratap
• Format: Article
• Language: English
• Subjects: Animals; Brain; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Critical period; Cypermethrin; Cytochrome P-450 CYP2E1 - biosynthesis; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins - biosynthesis; dopamine transporter; Enzymes; Female; Gene expression; Glutathione Transferase - biosynthesis; Lipid peroxidation; Lipid Peroxidation - drug effects; Male; Monoamine transporter; Neural Pathways - drug effects; Neural Pathways - metabolism; Neurodegeneration; Oxidative stress; Parkinson's disease; Pesticides - toxicity; Pregnancy; Pyrethrins - toxicity; Rats; Rats, Wistar; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Vesicular Monoamine Transport Proteins - biosynthesis; vesicular monoamine transporter 2
• ISSN: 1071-5762; 1029-2470
• DOI: 10.3109/10715762.2010.512041

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.