title: Carbofuran-induced neurochemical and neurobehavioral alterations in rats: attenuation by N-acetylcysteine.
abstract: Carbofuran, a widely used carbamate pesticide, has been reported to cause neurotoxicity. However, the underlying mechanisms involved in carbofuran neurotoxicity are not well understood. The present study was envisaged to investigate the possible role of oxidative stress in carbofuran neurotoxicity and to evaluate the protective effects of N-acetylcysteine (NAC). Acetylcholinesterase activity was significantly inhibited in all the regions of brain after carbofuran exposure (1 mg/kg body weight, orally, for 28 days). NAC, on the other hand, was found to partially restore the activity of acetylcholinesterase in carbofuran treated animals. Carbofuran exposure resulted in increased lipid peroxidation (LPO) in brain regions accompanied by decreased levels of glutathione. NAC administration to the carbofuran exposed animals lowered LPO along with partial repletion in glutathione levels. Concomitantly, the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were significantly decreased after carbofuran exposure, while no significant change in the activity of glutathione-S-transferase was observed. NAC treatment to carbofuran treated rats resulted in protective effect on the activities of these enzymes. Marked impairment in the motor function was seen following carbofuran exposure, which is evident by significant decrease in the retention time of the rats on rotating rods. Cognitive deficits were also seen after carbofuran exposure as indicated by the significant decrease in active avoidance response. NAC treatment significantly improved the carbofuran-induced neurobehavioral deficits. The results clearly demonstrate that carbofuran exerts its neurotoxic effects by accentuating oxidative stress and suggest neuroprotective role of NAC in carbofuran neurotoxicity.
authors.affiliation: Department of Biochemistry, Basic Medical Science Building, Panjab University, Chandigarh, 160014, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kamboj
authors.forename: Ravi
authors.initials: R
authors.lastname: Kiran
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000111:Acetylcysteine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects*; D002235:Carbofuran / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D045442:Rotarod Performance Test / Q000379:methods
chemical_list: D002800:Cholinesterase Inhibitors; D016166:Free Radical Scavengers; D000110:Acetylcholinesterase; D005978:Glutathione; D002235:Carbofuran; D000111:Acetylcysteine