Synergistic effect of selenium and melatonin on neuroprotection in cerebral ischemia in rats.
The synergistic scavenger effects of selenium and melatonin collectively we called Se-Mel was studied on the prevention of neuronal injury induced by ischemia/reperfusion. Male Wistar rats were treated with sodium selenite (0.1 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) 30 min before the middle carotid artery occlusion (MCAO) and immediately after MCAO to male Wistar rats and was continued for 3 days once daily at the interval of 24 h. Behavioral activity (spontaneous motor activity and motor deficit) was improved in Se-Mel-treated rats as compared to MCAO group rats. The level of glutathione and the activity of antioxidant enzymes was depleted significantly while the content of thiobarbituric acid reactive substances, protein carbonyl, and nitric oxide radical (NO(·)) was increased significantly in MCAO group. Systemic administration of Se-Mel ameliorated oxidative stress and improves ischemia/reperfusion-induced focal cerebral ischemia. Se-Mel also inhibited inducible nitric oxide synthase expression in Se-Mel+MCAO group as compared to MCAO group rats. Thus, Se-Mel has shown an excellent neuroprotective effect against ischemia/reperfusion injury through an anti-ischemic pathway. In conclusion, we demonstrated that the pretreatment with Se-Mel at the onset of reperfusion, reduced post-ischemic damage, and improved neurological outcome following transient focal cerebral ischemia in male Wistar rat.
Ahmad
Ajmal
A
Neurotoxicology laboratory, Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
Khan
Mohd Moshahid
MM
Ishrat
Tauheed
T
Khan
M Badruzzaman
MB
Khuwaja
Gulrana
G
Raza
Syed Shadab
SS
Shrivastava
Pallavi
P
Islam
Fakhrul
F
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000494:pharmacology / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D018696:Neuroprotective Agents; D017392:Thiobarbituric Acid Reactive Substances; D005978:Glutathione; D012643:Selenium; D008550:Melatonin