Parvez Suhel, Tabassum Heena, Banerjee Basu Dev, Raisuddin Sheikh
Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
Basic Clin Pharmacol Toxicol. 2008 Apr;102(4):382-7. doi: 10.1111/j.1742-7843.2008.00208.x. Epub 2008 Feb 29.
Tamoxifen is a selective oestrogen receptor modulator widely used in the treatment of breast cancer. Tamoxifen potentially affects mitochondrial functions as it acts as an uncoupling agent and a powerful inhibitor of mitochondrial electron transport chain. There is concern for the deleterious effects of tamoxifen. Taurine is known to have membrane stabilizing and antioxidant properties. We studied effect of taurine pre-treatment on the toxicity of tamoxifen in mouse liver mitochondria focusing specifically on the redox cycle biomarkers. Tamoxifen caused a significant rise in the mitochondrial lipid peroxidation, protein carbonyl content and superoxide radical generation. There was a significant change in the mitochondrial thiol profile in the tamoxifen-treated animals. Pre-treatment of mice with taurine (100 mg/kg) markedly lowered mitochondrial lipid peroxidation, protein carbonyl content and superoxide radical generation. It also restored decreased enzymatic and non-enzymatic antioxidants of mitochondria. It is suggested that taurine has a potential role in ameliorating tamoxifen-induced mitochondrial toxicity, and the protection is afforded either by reversing the decline of antioxidants or by the direct free radical-scavenging activity.
他莫昔芬是一种广泛用于治疗乳腺癌的选择性雌激素受体调节剂。他莫昔芬可能会影响线粒体功能,因为它可作为解偶联剂和线粒体电子传递链的强效抑制剂。人们对他莫昔芬的有害影响表示担忧。已知牛磺酸具有膜稳定和抗氧化特性。我们研究了牛磺酸预处理对小鼠肝线粒体中他莫昔芬毒性的影响,特别关注氧化还原循环生物标志物。他莫昔芬导致线粒体脂质过氧化、蛋白质羰基含量和超氧自由基生成显著增加。在接受他莫昔芬治疗的动物中,线粒体硫醇谱有显著变化。用牛磺酸(100mg/kg)预处理小鼠可显著降低线粒体脂质过氧化、蛋白质羰基含量和超氧自由基生成。它还恢复了线粒体中降低的酶促和非酶促抗氧化剂水平。提示牛磺酸在改善他莫昔芬诱导的线粒体毒性方面具有潜在作用,这种保护作用可能是通过逆转抗氧化剂的下降或通过直接的自由基清除活性来实现的。