Cholinergic dysfunctions and enhanced oxidative stress in the neurobehavioral toxicity of lambda-cyhalothrin in developing rats.
This study is focused on understanding the mechanism of neurobehavioral toxicity of lambda-cyhalothrin, a new generation type II synthetic pyrethroid in developing rats following their exposure from post-lactational day (PLD)22 to PLD49 and investigate whether neurobehavioral alterations are transient or persistent. Post-lactational exposure to lambda-cyhalothrin (1.0 or 3.0 mg/kg body weight, p.o.) affected grip strength and learning activity in rats on PLD50 and the persistent impairment of grip strength and learning was observed at 15 days after withdrawal of exposure on PLD65. A decrease in the binding of muscarinic-cholinergic receptors in frontocortical, hippocampal, and cerebellar membranes associated with decreased expression of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in hippocampus was observed following exposure to lambda-cyhalothrin on PLD50 and PLD65. Exposure to lambda-cyhalothrin was also found to increase the expression of growth-associated protein-43 in hippocampus of rats on PLD50 and PLD65 as compared to controls. A significant increase in lipid peroxidation and protein carbonyl levels and decreased levels of reduced glutathione and activity of superoxide dismutase, catalase, and glutathione peroxidase in brain regions of lambda-cyhalothrin exposed rats were distinctly observed indicating increased oxidative stress. Inhibition of ChAT and AChE activity may cause down-regulation of muscarinic-cholinergic receptors consequently impairing learning activity in developing rats exposed to lambda-cyhalothrin. The data further indicate that long-term exposure to lambda-cyhalothrin at low doses may be detrimental and changes in selected behavioral and neurochemical end points may persist if exposure to lambda-cyhalothrin continues.
Developmental Toxicology, CSIR-Indian Institute of Toxicology Research, MG Marg, P.O. Box 80, Lucknow 226 001, India.
Reyaz W
RW
Ansari
Rajendra K
RK
Shukla
Rajesh S
RS
Yadav
Kavita
K
Seth
Aditya B
AB
Pant
Dhirendra
D
Singh
Ashok K
AK
Agrawal
Fakhrul
F
Islam
Vinay K
VK
Khanna
D000110:Acetylcholinesterase / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D018678:Cholinergic Agents / Q000378:metabolism*; D002658:Developmental Disabilities / Q000139:chemically induced / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000378:metabolism; D018737:Hand Strength / Q000502:physiology; D007306:Insecticides / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000150:complications / Q000209:etiology / Q000378:metabolism; D009570:Nitriles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000378:metabolism
D018678:Cholinergic Agents; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D011976:Receptors, Muscarinic; D002374:Catalase; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; D005978:Glutathione; C037304:cyhalothrin