Ezhilarasan Devaraj
Department of Pharmacology, Saveetha Dental College, Saveetha Institue of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu-600 077, India.
Arab J Gastroenterol. 2018 Jun;19(2):56-64. doi: 10.1016/j.ajg.2018.03.002. Epub 2018 May 28.
Oxidative stress plays an important role in the pathogenesis of various chronic liver diseases (CLD) and increasing evidence have confirmed the contributory role of oxidative stress in the pathogenesis of drugs and chemical-induced CLD. Chronic liver injury is manifested as necrosis, cholestasis, fibrosis, and cirrhosis. Chronic administration of anti-tubercular, anti-retroviral, immunosuppressive drugs is reported to induce free radical generation during their biotransformation in the liver. Further, these reactive intermediates are said to induce profibrogenic cytokines, several inflammatory markers, collagen synthesis during the progression of hepatic fibrosis. Oxidative stress and free radicals are reported to induce activation and proliferation of hepatic stellate cells in the injured liver leading to the progression of CLD. Hence, to counteract or to scavenge these reactive intermediates, several plant-derived antioxidant principles have been effectively employed against oxidative stress and came out with promising results in human and experimental models of CLD. This review summarizes the relationships between oxidative stress and different liver pathogenesis induced by drugs and xenobiotics, focusing upon different chronic liver injury induced by alcohol, antitubercular drugs and hyperactivity of antiretroviral drugs in HIV patients, viral hepatitis infection induced oxidative stress.
氧化应激在各种慢性肝病(CLD)的发病机制中起重要作用,越来越多的证据证实氧化应激在药物和化学物质诱导的CLD发病机制中起作用。慢性肝损伤表现为坏死、胆汁淤积、纤维化和肝硬化。据报道,长期使用抗结核、抗逆转录病毒、免疫抑制药物在肝脏生物转化过程中会诱导自由基生成。此外,据说这些反应性中间体在肝纤维化进展过程中会诱导促纤维化细胞因子、多种炎症标志物和胶原蛋白合成。据报道,氧化应激和自由基会诱导受损肝脏中肝星状细胞的激活和增殖,导致CLD进展。因此,为了对抗或清除这些反应性中间体,几种植物源性抗氧化剂已被有效地用于对抗氧化应激,并在CLD的人体和实验模型中取得了有希望的结果。这篇综述总结了氧化应激与药物和异源生物诱导的不同肝脏发病机制之间的关系,重点关注酒精、抗结核药物和HIV患者抗逆转录病毒药物活性过高引起的不同慢性肝损伤,以及病毒肝炎感染诱导的氧化应激。