Nagai Katsuhito, Fukuno Shuhei, Oda Ayano, Konishi Hiroki
Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Japan.
Anticancer Drugs. 2016 Jan;27(1):17-23. doi: 10.1097/CAD.0000000000000299.
The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppressive effects of taurine in terms of alterations in oxidative stress and apoptotic responses. DOX-induced body weight loss was completely suppressed by taurine treatment. Elevations in the serum activity levels of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase by DOX were also dose-dependently attenuated by a concurrent treatment with taurine. Superoxide dismutase activity and reduced glutathione content in the liver were decreased following the administration of DOX, whereas these changes were suppressed when 10 mg/kg taurine was given in combination with DOX. Taurine attenuated the increased expression of mRNAs for Fas and Bax after DOX exposure. Furthermore, the formation of cleaved caspase-3 protein in the group given DOX with taurine was lower than that in the group treated with DOX alone. Our results suggest that taurine can protect against DOX-induced acute hepatic damage, the underlying mechanism of which is attributable to the suppression of oxidative stress and apoptotic responses.
阿霉素(DOX)是一种蒽环类抗肿瘤药物,尽管其具有临床应用价值,但其器官毒性限制了治疗窗口。在本研究中,我们确定了牛磺酸是否能预防DOX诱导的肝损伤,并从氧化应激和凋亡反应的改变方面探讨了牛磺酸抑制作用的分子机制。牛磺酸治疗完全抑制了DOX诱导的体重减轻。DOX导致的乳酸脱氢酶、天冬氨酸转氨酶和丙氨酸转氨酶血清活性水平升高也因同时给予牛磺酸而呈剂量依赖性减弱。给予DOX后,肝脏中超氧化物歧化酶活性和还原型谷胱甘肽含量降低,而当与DOX联合给予10 mg/kg牛磺酸时,这些变化受到抑制。牛磺酸减弱了DOX暴露后Fas和Bax mRNA表达的增加。此外,给予DOX和牛磺酸组中裂解的caspase-3蛋白的形成低于单独给予DOX组。我们的结果表明,牛磺酸可以预防DOX诱导的急性肝损伤,其潜在机制是抑制氧化应激和凋亡反应。