title: Effect of phosphamidon on cognition and oxidative stress and its modulation by ascorbic acid and 4'-chlorodiazepam in rats.
abstract: Neurosteroids and micronutrient are known to possess neuromodulator and neuroprotective activities. The present study was designed to investigate the effect of 4'-chlorodiazepam (4CD) or ascorbic acid (Vit C) on phosphamidon (PM) induced modulation of cognitive function and oxidative stress in male Wistar rats. Cognitive function was measured by using step-down latency (SDL) on a continuous avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was estimated by measuring brain malondialdehyde (MDA) level, protein carbonyl (PC) and reduced glutathione (GSH) activity. A significant reduction in both acquisition and retention in SDL was found for the PM treated group at weeks 6 and 8 as compared to the control (p<0.001). PM caused a significant prolongation in both acquisition and retention in TL at 6 and 8 weeks as compared to the control (p<0.001). Two-week treatment of 4CD or Vit C antagonized the effect of PM on SDL and TL at 8th week. PM produced a statistically significant increase in the brain MDA and PC levels (p<0.001) and a significant decrease in the brain GSH activity (p<0.001). Treatment with 4CD or Vit C attenuated the effect of PM on MDA, PC and GSH activities. Results of this study suggest that Vit C and 4CD have potential in reversing cognitive dysfunction and oxidative stress induced by toxicants like PM in the brain.
authors.affiliation: Department of Biotechnology, Priyadarshini Institute of Engineering and Technology, Nagpur 440 019, India. sgsuke@hotmail.com
authors.forename: Sanvidhan G
authors.initials: SG
authors.lastname: Suke
authors.forename: Anand
authors.initials: A
authors.lastname: Shukla
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Mundhada
authors.forename: B D
authors.initials: BD
authors.lastname: Banerjee
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Mediratta
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001570:Benzodiazepinones / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D004347:Drug Interactions; D007306:Insecticides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010707:Phosphamidon / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001570:Benzodiazepinones; D002352:Carrier Proteins; D007306:Insecticides; D011963:Receptors, GABA-A; D010707:Phosphamidon; C069997:Tspo protein, rat; C028513:4'-chlorodiazepam; D001205:Ascorbic Acid