Reversal of propoxur-induced impairment of memory and oxidative stress by 4'-chlorodiazepam in rats.
Carbamate pesticides like propoxur have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was designed to explore the modulation of the effects of propoxur over cognitive function by progesterone (PROG) and 4'-chlorodiazepam (4CD). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus, transfer latency (TL) on a plus maze and spatial navigation test on Morris water maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and reduced glutathione (GSH) levels and catalase (CAT) activity. A significant reduction in SDL and prolongation of TL and spatial navigation test was found for the propoxur (10 mg/kg/d; p.o.) treated group at weeks 6 and 7 as compared with control. One-week treatment with 4CD (0.5 mg/kg/d; i.p.) antagonized the effect of propoxur on SDL, spatial navigation test as well as TL; whereas, PROG failed to modulate this effect at a dose of 15 mg/kg/d, i.p. Propoxur produced a statistically significant increase in the brain MDA levels and decrease in the brain GSH levels and CAT activity. Treatment with 4CD at the above dose attenuated the effect of propoxur on oxidative stress whereas PROG (15 mg/kg/d; i.p.) failed to influence the same. The results of the present study thus show that 4-CD has the potential to attenuate cognitive dysfunction and oxidative stress induced by toxicants like propoxur in the brain.
Mehta
Kapil Dev
KD
Department of Pharmacology, University College of Medical Sciences, University of Delhi, Delhi, 110095, India.
Garg
Gobind Rai
GR
Mehta
Ashish K
AK
Arora
Tarun
T
Sharma
Amit K
AK
Khanna
Naresh
N
Tripathi
Ashok K
AK
Sharma
Krishna K
KK
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D001074:Propoxur / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D001570:Benzodiazepinones; C028513:4'-chlorodiazepam; D001074:Propoxur