Department of Biophysics, Panjab University, Chandigarh 160014, India.
Toxicol Mech Methods. 2010 Feb;20(2):82-9. doi: 10.3109/15376510903559950.
It is widely accepted that oxidative stress plays a central role in alcohol-induced pathogenesis. Redox-sensitive transcription factors nuclear factor-kappaB (NFkappaB) and activator protein-1 (AP1) are involved in development of alcohol-related diseases. Because of its antioxidative properties, vitamin E is believed to prevent diseases associated with oxidative stress. The aim of the present study was to evaluate the molecular mechanism associated with alcohol-induced oxidative stress and its prevention with vitamin E supplementation. Male Balb/c mice were divided into three groups viz. group I (control), group II (alcohol-treated) and group III (alcohol-treated + Vitamin E supplemented). Group II received 8% alcohol as sole source of drinking fluid while group III was given Vitamin E orally as 5 IU/kg body weight along with 8% alcohol. After 15 days, increases in lipid peroxidation, catalase and GST activity and decreases in SOD activity as well as redox ratio were observed in group II. This was associated with increased apoptosis in this group. Vitamin E supplementation restored the redox status, reduced apoptosis and prevented oxidative stress. Further mRNA expression of cjun, cfos, p65 (NFkappaB) showed increased expression during oxidative stress in group II. Although inhibition in NFkappaB activation was observed with Vitamin E, on the contrary it stimulated AP1 expression. This study supports the fact that alcohol promoted oxidative stress and is the major cause of alcohol toxicity in liver. Vitamin E can mitigate the toxic effects of alcohol and can be suitably used as a potential therapeutic agent for alcohol-induced oxidative damage in liver.
普遍认为，氧化应激在酒精引起的发病机制中起着核心作用。氧化还原敏感转录因子核因子-κB（NFκB）和激活蛋白-1（AP1）参与了与酒精相关疾病的发展。由于其抗氧化特性，维生素 E 被认为可以预防与氧化应激相关的疾病。本研究旨在评估与酒精诱导的氧化应激相关的分子机制及其通过补充维生素 E 进行预防。雄性 Balb/c 小鼠分为三组：I 组（对照组）、II 组（酒精处理组）和 III 组（酒精处理+维生素 E 补充组）。II 组仅接受 8%酒精作为唯一的饮水源，而 III 组则口服给予 5IU/kg 体重的维生素 E 以及 8%酒精。15 天后，II 组的脂质过氧化、过氧化氢酶和 GST 活性增加，SOD 活性以及氧化还原比降低，同时观察到细胞凋亡增加。维生素 E 补充恢复了氧化还原状态，减少了细胞凋亡，并预防了氧化应激。进一步的 cjun、cfos、p65（NFκB）mRNA 表达显示，在 II 组的氧化应激过程中表达增加。尽管维生素 E 抑制了 NFκB 的激活，但它反而刺激了 AP1 的表达。这项研究支持了这样一个事实，即酒精促进了氧化应激，是肝脏中酒精毒性的主要原因。维生素 E 可以减轻酒精的毒性作用，并可作为一种潜在的治疗剂，用于治疗肝脏中由酒精引起的氧化损伤。
