Protective effects of carbenoxolone are associated with attenuation of oxidative stress in ischemic brain injury.
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ABSTRACT:
SUBMITTER: Zhang L
PROVIDER: S-EPMC5561849 | biostudies-other | 2013 Jun
REPOSITORIES: biostudies-other
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Project description:CONTEXT:Hypoxic-ischemic encephalopathy (HIE) has a high morbidity and mortality rate. Resveratrol possesses numerous biological properties including antioxidant, anti-inflammatory and neuroprotective activities. OBJECTIVE:The current experiment investigates the neuroprotective efficacy of resveratrol (RESV) against HIE by modulating Nrf2/HO-1 pathway in neonatal rats. MATERIALS AND METHODS:Seven-day-old pups (n?=?48) were divided into four groups. Group-I rats receiving 2% DMSO saline (sham), group-II rats underwent unilateral carotid artery ligation and hypoxia (92% N2 and 8% O2) for 2.5?h (hypoxia-ischemia; HI), group-III and IV rats received 20 (RESV 20?+?HI) or 40?mg/kg (RESV 40?+?HI; group-IV) of RESV via intraperitoneal injection (ip), respectively, for 7?days prior to HI induction. RESULTS:Pre-treatment with RESV (20 or 40) markedly reduced (p?<?0.01) the cerebral oedema (86.23-71.26 or 65.24%), infarct area (33.85-19.81 or 14.30%), lipid peroxidation products, inflammatory markers [IL-1? 186-110 or 82; IL-6 255-146 or 103; TNF-? 310-204 or 137; NF-?B 205-115 or 91) p65 subunit] and significantly restored (p?<?0.01) the antioxidative status by enhancing the activities of glutathione peroxidase (GPx) 5.22-6.49 or 7.78; catalase (CAT) 51-55 or 59, superoxide dismutase (SOD) 2.5-3.05 or 3.25; through marked upregulation (p?<?0.01) of heme oxygenase 1 (HO-1) 0.65-0.69 or 0.73; and nuclear factor erythroid 2 related factor 2 (Nrf2) 0.73-0.86 or 0.91. DISCUSSION AND CONCLUSIONS:RESV displays its neurotherapeutic potential via upregulating the protein expression of Nrf2 and HO-1 signalling pathway and thereby attenuates oxidative stress and inflammatory response in HI-induced neonatal rats.
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