State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China; Department of Pharmacy, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, 215153, China.
Free Radic Biol Med. 2024 Aug 1;220:236-248. doi: 10.1016/j.freeradbiomed.2024.05.003. Epub 2024 May 3.
Alcoholic liver disease (ALD) is a common chronic redox disease caused by increased alcohol consumption. Abstinence is a major challenge for people with alcohol dependence, and approved drugs have limited efficacy. Therefore, this study aimed to explore a new treatment strategy for ALD using ferroferric oxide endohedral fullerenol (FeO@C(OH)) in combination with static magnetic and electric fields (sBE). The primary hepatocytes of 8-9-week-old female BALB/c mice were used to evaluate the efficacy of the proposed combination treatment. A mouse chronic binge ethanol feeding model was established to determine the alleviatory effect of FeO@C(OH) on liver injury under sBE exposure. Furthermore, the ability of FeO@C(OH) to eliminate •OH was evaluated. Alcohol-induced hepatocyte and mitochondrial damage were reversed in vitro. Additionally, the combination therapy reduced liver damage, alleviated oxidative stress by improving antioxidant levels, and effectively inhibited liver lipid accumulation in animal experiments. Here, we used a combination of magnetic derivatives of fullerenol and sBE to further improve the ROS clearance rate, thereby alleviating ALD. The developed combination treatment may effectively improve alcohol-induced liver damage and maintain redox balance without apparent toxicity, thereby enhancing therapy aimed at ALD and other redox diseases.
酒精性肝病(ALD)是一种由饮酒量增加引起的常见慢性氧化还原疾病。戒酒对于酒精依赖的人来说是一个主要的挑战,而经过批准的药物疗效有限。因此,本研究旨在探索使用内包铁氧化物富勒醇(FeO@C(OH))结合静磁场和电场(sBE)治疗 ALD 的新策略。使用 8-9 周龄雌性 BALB/c 小鼠的原代肝细胞来评估所提出的联合治疗的疗效。建立了小鼠慢性 binge 乙醇喂养模型,以确定 FeO@C(OH) 在 sBE 暴露下对肝损伤的缓解作用。此外,还评估了 FeO@C(OH) 消除 •OH 的能力。在体外,酒精诱导的肝细胞和线粒体损伤得到逆转。此外,该联合治疗在动物实验中降低了肝损伤,通过提高抗氧化水平缓解氧化应激,并有效抑制肝脏脂质积累。在这里,我们使用富勒醇的磁衍生物和 sBE 的组合来进一步提高 ROS 清除率,从而缓解 ALD。所开发的联合治疗可能会有效改善酒精引起的肝损伤并维持氧化还原平衡,而没有明显的毒性,从而增强针对 ALD 和其他氧化还原疾病的治疗。