Shettigar Nishan B, Das Shubhankar, Rao Nageshwar B, Rao Satish B S
Department of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka, 576 104, India.
Division of Radiobiology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, 576 104, India.
Environ Toxicol. 2015 Jul 8;30(8):968-80. doi: 10.1002/tox.21971. Epub 2014 Feb 27.
Thymol (TOH) was investigated for its ability to protect against mercuric chloride (HgCl2 )-induced cytotoxicity and genotoxicity using human hepatocarcinoma (HepG2) cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay confirmed the efficacy of TOH pretreatment in attenuating HgCl2 -induced cytotoxicity. Pretreatment with TOH inhibited HgCl2 -induced genotoxicity, depolarization of mitochondrial membrane, oxidative stress, and mitochondrial superoxide levels. Interestingly, TOH (100 µM) alone elevated the intracellular basal glutathione S-transferase (GST) levels and TOH pretreatment abrogated the decrease in glutathione, GST, superoxide dismutase, and catalase levels even after HgCl2 intoxication. Furthermore, TOH was also capable of inhibiting HgCl2 -induced apoptotic as well as necrotic cell death analyzed by flowcytometric analysis of cells dual stained with Annexin-FITC/propidium iodide. The present findings clearly indicate the cytoprotective potential of TOH against HgCl2 -induced toxicity, which may be attributed to its free radical scavenging ability which facilitated in reducing oxidative stress and mitochondrial damage thereby inhibiting cell death.
使用人肝癌(HepG2)细胞系研究了百里酚(TOH)抵御氯化汞(HgCl2)诱导的细胞毒性和遗传毒性的能力。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐检测证实了TOH预处理减轻HgCl2诱导的细胞毒性的功效。TOH预处理抑制了HgCl2诱导的遗传毒性、线粒体膜去极化、氧化应激和线粒体超氧化物水平。有趣的是,单独的TOH(100µM)提高了细胞内基础谷胱甘肽S-转移酶(GST)水平,并且即使在HgCl2中毒后,TOH预处理也消除了谷胱甘肽、GST、超氧化物歧化酶和过氧化氢酶水平的降低。此外,通过用膜联蛋白-FITC/碘化丙啶双重染色的细胞进行流式细胞术分析,TOH还能够抑制HgCl2诱导的凋亡以及坏死性细胞死亡。目前的研究结果清楚地表明了TOH对HgCl2诱导的毒性的细胞保护潜力,这可能归因于其自由基清除能力,该能力有助于减少氧化应激和线粒体损伤,从而抑制细胞死亡。