Ito Takashi, Muraoka Satoko, Takahashi Kyoko, Fujio Yasushi, Schaffer Stephen W, Azuma Junichi
Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
Adv Exp Med Biol. 2009;643:65-74. doi: 10.1007/978-0-387-75681-3_7.
Though the administration of taurine is clinically efficacious against heart failure, the mechanism underlying its cardioprotection remains to be established. To provide information on the mechanism, we examined the effects of taurine on doxorubicin (DOX)-induced cardiotoxicity, with an emphasis on ROS generation and cardiac gene inhibition. Oral administration of taurine (3% w/v in tap water) dramatically reduced the mortality rate in both the acute or sub-acute toxic models of DOX toxicity. It was shown that taurine prevented DOX-induced oxidative stress as determined from cardiac glutathione content. Interestingly, Northern blot analysis revealed that DOX altered cardiac gene expression, including that of alpha-myosin heavy chain, ventricular myosin light chain-2 isoform and brain natriuretic peptide, an effect partially ameliorated by taurine treatment. In conclusion, taurine suppresses ROS generation and regulates gene expression in the DOX treated heart.
尽管牛磺酸在临床上对心力衰竭有效，但其心脏保护作用的潜在机制仍有待确定。为了提供有关该机制的信息，我们研究了牛磺酸对阿霉素（DOX）诱导的心脏毒性的影响，重点关注活性氧生成和心脏基因抑制。口服牛磺酸（自来水中3% w/v）显著降低了DOX毒性急性或亚急性毒性模型中的死亡率。结果表明，从心脏谷胱甘肽含量测定来看，牛磺酸可预防DOX诱导的氧化应激。有趣的是，Northern印迹分析显示，DOX改变了心脏基因表达，包括α-肌球蛋白重链、心室肌球蛋白轻链-2亚型和脑钠肽的表达，牛磺酸治疗可部分改善这种影响。总之，牛磺酸可抑制DOX处理的心脏中的活性氧生成并调节基因表达。
