Effect of progesterone on phosphamidon-induced impairment of memory and oxidative stress in rats.
Progesterone (a neurosteroid) is an important modulator of the nervous system functioning. Organophosphorus pesticides like phosphamidon have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was therefore designed to investigate the effects of progesterone (PROG) on phosphamidon-induced modulation of cognitive function and oxidative stress in rats. 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 thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the phosphamidon (1.74 mg/kg/d; p.o.) treated group at weeks 6 and 8 as compared to the control group. Two weeks treatment with PROG (15 mg/kg/d; i.p.) antagonized the effect of phosphamidon on SDL as well as TL. Phosphamidon alone produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. Treatment with PROG (15 mg/kg/d; i.p.) attenuated the effect of phosphamidon on oxidative stress. Together, the results showed that progesterone attenuated the cognitive dysfunction and increased oxidative stress induced by phosphamidon in the brain.
Department of Pharmacology, University College of Medical Sciences (University of Delhi), Delhi, India.
Amit K
AK
Sharma
Swapan K
SK
Bhattacharya
Naresh
N
Khanna
Ashok K
AK
Tripathi
Tarun
T
Arora
Ashish K
AK
Mehta
Kapil D
KD
Mehta
Vikas
V
Joshi
D000818:Animals; D001362:Avoidance Learning; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D010707:Phosphamidon / Q000633:toxicity*; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D007306:Insecticides; D011372:Progestins; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D010707:Phosphamidon; D011374:Progesterone