Resveratrol mitigates the oxidative stress mediated by hypoxic-ischemic brain injury in neonatal rats via Nrf2/HO-1 pathway

• Main Authors: Yan Gao, Rongrong Fu, Jue Wang, Xue Yang, Lulu Wen, Juan Feng
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2018-01-01
• Series: Pharmaceutical Biology
• Subjects: lipid peroxidation; inflammatory markers; infarct area; oedema; neurotherapeutic
• Online Access: http://dx.doi.org/10.1080/13880209.2018.1502326

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-1β 186–110 or 82; IL-6 255–146 or 103; TNF-α 310–204 or 137; NF-κB 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.