Protective effect of exogenous administration of alpha-tocopherol in middle cerebral artery occlusion model of cerebral ischemia in rats.
Oxidative stress due to increased free radical generation and depletion of endogenous antioxidants have been implicated in ischemia-reperfusion-induced neuronal injury. The present study was carried out to study the effect of acute administration of alpha-tocopherol in the middle cerebral artery (MCA) occlusion model of stroke in rats. Rats were anesthetized using chloral hydrate (400 mg/kg i.p.) and subjected to 2 h of transient MCA occlusion. alpha-Tocopherol was administered at the dose of 125 and 250 mg/kg orally 1 h prior to the occlusion of MCA. Motor performance test (grip test, foot fault test, rotarod performance test, spontaneous locomotor activity), markers of oxidative stress and 2,3,5-triphenyl tetrazolium chloride staining were carried out 24 h after MCA occlusion. A vehicle-treated group was run parallel. It was observed that alpha-tocopherol at the dose of 125 mg/kg neither improved neurologic deficit, nor decreased the raised level of oxidative stress markers in comparison with the MCA-occluded rats. However, higher dose of alpha-tocopherol (250 mg/kg p.o.) afforded significant protection as evident by increase in motor performance tests and a decrease in the volume of infarction. The raised levels of malondialdehyde after MCA occlusion were also significantly attenuated. The results demonstrate that exogenous administration of alpha-tocopherol is able to reduce the neuronal damage caused during ischemia-reperfusion, which can be attributed to its antioxidant activity.
Chaudhary
Geeta
G
Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India.
Sinha
Kusum
K
Gupta
Y K
YK
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018737:Hand Strength / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000037:antagonists & inhibitors / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D045442:Rotarod Performance Test; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000975:Antioxidants; D008315:Malondialdehyde; D024502:alpha-Tocopherol