title: Protective effect of grape seed and skin extract on cerebral ischemia in rat: implication of transition metals.
abstract: Ischemic stroke is a leading cause of long lasting disability in humans and oxidative stress an important underlying cause. The present study aims to determine the effect of short term (seven-days) administration of high dosage grape seed and skin extract (GSSE 2.5 g/kg) on ischemia/reperfusion (I/R) injury in a rat model of global ischemia. Ischemia was induced by occlusion of the common carotid arteries for 30 min followed by one-hour reperfusion on control or GSSE treated animals. I/R induced a drastic oxidative stress characterized by high lipid and protein oxidation, a drop in antioxidant enzyme defenses, disturbed transition metals as free iron overload and depletion of copper, zinc and manganese as well as of associated brain enzyme activities as glutamine synthetase and lactate dehydrogenase. I/R also induced NO and calcium disruption and an increase in calpain activity, a calcium-sensitive cysteine protease. Interestingly, almost all I/R-induced disturbances were prevented by GSSE pretreatment as oxidative stress, transition metals associated enzyme activities, brain damage size and histology. Owing to its antioxidant potential, high dosage GSSE protected efficiently the brain against ischemic stroke and should be translated to humans.
authors.affiliation: Bioactive Substance Laboratory, Biotechnology Centre, Hammam-Lif, Tunis.
authors.forename: Kadri
authors.initials: K
authors.lastname: Safwen
authors.forename: Smine
authors.initials: S
authors.lastname: Selima
authors.forename: Elayed
authors.initials: E
authors.lastname: Mohamed
authors.forename: Limam
authors.initials: L
authors.lastname: Ferid
authors.forename: Cosette
authors.initials: C
authors.lastname: Pascal
authors.forename: Amri
authors.initials: A
authors.lastname: Mohamed
authors.forename: Aouani
authors.initials: A
authors.lastname: Ezzedine
authors.forename: Mokni
authors.initials: M
authors.lastname: Meherzia
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D002544:Cerebral Infarction / Q000209:etiology; D005260:Female; D008315:Malondialdehyde / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications; D012639:Seeds / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D009573:Nitrites; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D010088:Oxidoreductases; D002154:Calpain; D002118:Calcium
keywords: GSSE; antioxidant activity; brain; calpain; ischemia; transition metal