Involvement of nitric oxide in the protective effects of dehydroepiandrosterone sulphate on stress induced neurobehavioral suppression and brain oxidative injury in rats.
The involvement of nitric oxide (NO) in the effects of dehydroepiandrosterone sulphate (DHEAS) on restraint stress induced neurobehavioral and brain oxidative/nitrosative stress markers was investigated in rats. Exposure of rats to restraint stress suppressed behavioral activity in the elevated plus maze and this was associated with increases in malondialdehyde (MDA) and decrease in reduced glutathione (GSH) and brain NO metabolite (NOx) levels in brain homogenates. Pretreatment with DHEAS (5-40mg/s.c.) reversed the stress induced changes in behavioral and oxidative stress markers and also brain NOx levels. The beneficial effect of DHEAS (40mg/kgs.c.) was blocked by pretreatment with nitric oxide synthase inhibitor, L-NAME (50mg/kgi.p.) while pretreatment of rats with NO-precursor l-Arginine (100mg/kg i.p.) produced potentiation of action of sub effective dose of DHEAS (5mg/kgs.c.). The DHEAS effects were stress specific as these behavioral and biochemical parameters were not much influenced in non-stressed rats. These observations suggest that pretreatment with DHEAS has a protective effect on restraint stress induced alteration of neurobehavioral changes and brain oxidative injury in rats and NO-dependent mechanisms may be involved in this effect.
department of Pharmacy,Vallabhbhai Patel Chest Institute, University of Delhi, India.
Ayanabha
A
Chakraborti
Kavita
K
Gulati
Arunabha
A
Ray
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology / Q000528:radiation effects* / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000187:drug effects*
D009569:Nitric Oxide; D008315:Malondialdehyde; D019314:Dehydroepiandrosterone Sulfate; D005978:Glutathione