Division of Toxicology, Central Drug Research Institute, Lucknow 262 001, (CSIR) India.
Toxicol Mech Methods. 2010 Jun;20(5):242-51. doi: 10.3109/15376511003793325.
Isoniazid (INH) is a first-line antibiotic used in the treatment of infections caused by Mycobacterium tuberculosis. However it has a serious limitation of being hepatotoxic. Delineating the mechanism underlying INH-induced hepatotoxicity may be beneficial in devising ways to counteract its toxic manifestations. Studies in human hepatoma HepG2 cells have indicated that INH exposure causes induction of apoptosis. This study was aimed at identifying the key components/pathways of the INH-induced apoptotic pathway using HepG2 cells. HepG2 cells were exposed to increasing concentrations of INH (6.5, 13, 26, and 52 mM). Hydrogen peroxide (0.3 mM) served as positive control. After incubating for specific time intervals cells were harvested and evidences of cytotoxicity, oxidative stress, and apoptosis were sought. The findings indicated that INH exposure causes increased ROS generation along with alteration in levels of enzymatic antioxidants such as Superoxide dismutase, Catalase, and Glucose-6-Phosphate dehydrogenase. Altered Bcl-2/Bax content, cytochrome-c translocation, caspase activation, and DNA fragmentation emphasized involvement of apoptosis.
异烟肼（INH）是一种用于治疗结核分枝杆菌感染的一线抗生素。然而，它有一个严重的局限性，即具有肝毒性。阐明 INH 诱导肝毒性的机制可能有助于设计对抗其毒性表现的方法。在人肝癌 HepG2 细胞中的研究表明，INH 暴露会导致细胞凋亡的诱导。本研究旨在使用 HepG2 细胞鉴定 INH 诱导的凋亡途径的关键组成部分/途径。将 HepG2 细胞暴露于递增浓度的 INH（6.5、13、26 和 52mM）。过氧化氢（0.3mM）用作阳性对照。孵育特定时间间隔后，收获细胞并寻找细胞毒性、氧化应激和细胞凋亡的证据。研究结果表明，INH 暴露会导致 ROS 生成增加，同时改变超氧化物歧化酶、过氧化氢酶和葡萄糖-6-磷酸脱氢酶等酶抗氧化剂的水平。Bcl-2/Bax 含量的改变、细胞色素 c 易位、半胱天冬酶激活和 DNA 片段化强调了细胞凋亡的参与。
