title: Melatonin attenuates cognitive dysfunction and reduces neural oxidative stress induced by phosphamidon.
abstract: Melatonin is an important modulator of nervous system functioning and important neural antioxidant. Organophosphate pesticides like phosphamidon (PHOS) have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. This study was designed to explore the modulation of the effects of PHOS on cognitive function by melatonin (MEL). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the PHOS (1.74 mg/kg/day; p.o.)-treated group at weeks 6 and 8 as compared to the control group. Two-week treatment with MEL (5 mg/kg/day; i.p.) antagonized the effect of PHOS on SDL as well as TL. PHOS alone produced a significant increase in the brain MDA levels and decrease in the brain NP-SH levels. Treatment with MEL attenuated the effect of PHOS on oxidative stress. Together the results showed that MEL attenuated the cognitive dysfunction and decreased oxidative stress induced by PHOS in the brain.
authors.affiliation: Department of Pharmacology, University College of Medical Sciences, University of Delhi, Delhi 110095, India.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Mehta
authors.forename: Naveen
authors.initials: N
authors.lastname: Rathor
authors.forename: Mahendra Kumar
authors.initials: MK
authors.lastname: Chalawadi Hanumantappa
authors.forename: Naresh
authors.initials: N
authors.lastname: Khanna
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004347:Drug Interactions; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010707:Phosphamidon / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D013438:Sulfhydryl Compounds; D010707:Phosphamidon; D008315:Malondialdehyde; D008550:Melatonin