Effects of cypermethrin on monoamine transporters, xenobiotic metabolizing enzymes and lipid peroxidation in the rat nigrostriatal system.
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.
Tiwari
Manindra Nath
MN
Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), M. G. Marg, Post Box 80, Lucknow 226 001, India.
Singh
Anand Kumar
AK
Ahmad
Israr
I
Upadhyay
Ghanshyam
G
Singh
Dhirendra
D
Patel
Devendra Kumar
DK
Singh
Chetna
C
Prakash
Om
O
Singh
Mahendra Pratap
MP
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000096:biosynthesis*; D005260:Female; D005982:Glutathione Transferase / Q000096:biosynthesis*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D010575:Pesticides / Q000633:toxicity*; D011247:Pregnancy; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000096:biosynthesis*
D050483:Dopamine Plasma Membrane Transport Proteins; D010575:Pesticides; D011722:Pyrethrins; D050493:Vesicular Monoamine Transport Proteins; C017160:cypermethrin; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; D004298:Dopamine