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Neuroprotective effects of ()-epigallocatechin gallate after hypoxia-ischemia-induced brain damage: novel mechanisms of action

Citation

Sutherland, BA and Shaw, OM and Clarkson, AN and Jackson, DM and Sammut, IA and Appleton, I, Neuroprotective effects of (-)-epigallocatechin gallate after hypoxia-ischemia-induced brain damage: novel mechanisms of action, The FASEB Journal, 19, (2) pp. 258-260. ISSN 1530-6860 (2005) [Refereed Article]

Copyright Statement

Copyright 2004 FASEB

DOI: doi:10.1096/fj.04-2806fje

Abstract

()-Epigallocatechin gallate (EGCG) is a potent antioxidant that is neuroprotective against ischemia-induced brain damage. However, the neuroprotective effects and possible mechanisms of action of EGCG after hypoxia-ischemia (HI) have not been investigated. Therefore, we used a modified "Levine" model of HI to determine the effects of EGCG. Wistar rats were treated with either 0.9% saline or 50 mg/kg EGCG daily for 1 day and 1 h before HI induction and for a further 2 days post-HI. At 26-days-old, both groups underwent permanent left common carotid artery occlusion and exposure to 8% oxygen/92% nitrogen atmosphere for 1 h. Histological assessment showed that EGCG significantly reduced infarct volume (38.016.4 mm3 ) in comparison to HI + saline (99.615.6 mm3 ). In addition, EGCG significantly reduced total (622.685.8 pmol L-[3 H]citrulline/30 min/mg protein) and inducible nitric oxide synthase (iNOS) activity (143.277.3 pmol L-[3 H]citrulline/30 min/mg protein) in comparison to HI+saline controls (996.6113.6 and 329.759.6 pmol L-[3 H]citrulline/30 min/mg protein for total NOS and iNOS activity, respectively). Western blot analysis demonstrated that iNOS protein expression was also reduced. In contrast, EGCG significantly increased endothelial and neuronal NOS protein expression compared with HI controls. EGCG also significantly preserved mitochondrial energetics (complex I-V) and citrate synthase activity. This study demonstrates that the neuroprotective effects of EGCG are, in part, due to modulation of NOS isoforms and preservation of mitochondrial complex activity and integrity. We therefore conclude that the in vivo neuroprotective effects of EGCG are not exclusively due to its antioxidant effects but involve more complex signal transduction mechanisms.

Item Details

Item Type:Refereed Article
Keywords:EGCG, NOS, ROS
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Medical and Health Sciences
Author:Sutherland, BA (Dr Brad Sutherland)
ID Code:113424
Year Published:2005
Web of Science® Times Cited:18
Deposited By:Office of the School of Medicine
Deposited On:2016-12-22
Last Modified:2017-05-11
Downloads:0

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