Department of Comparative Pathophysiology, Division of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
J Toxicol Sci. 2013;38(3):495-502. doi: 10.2131/jts.38.495.
The in vitro effects of 2 representative mycotoxins, T-2 toxin and deoxynivalenol (DON), of trichothecene group on the electron transport system (ETS) of mitochondria in rat cardiomyocytes were investigated by measuring oxygen consumption rates (OCR). The ATP-linked OCR and the reserve capacity (RC) of the mitochondria ETS were quantified by a "mitochondria stress test" which was estimated by the OCR responses to oligomycin and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone, with an extracellular flux analyzer. The basal OCR was significantly inhibited by the application of T-2 toxin at concentrations of 6 × 10⁻¹ to 6 × 10⁻⁵ μM and DON at concentrations of 0.78 to 100 μM for 24 hr. The threshold of cardiomyocyte toxicity was estimated to be between 6.0 × 10⁻⁶ and 6.0 × 10⁻⁵ μM for T-2 toxicity on both ATP-linked OCR and RC and between 0.39 and 0.78 μM on ATP-linked OCR or between 1.56 and 3.13 μM on RC for DON. The decrease in OCR of cardiomyocytes exposed to T-2 toxin with a concentration of 6.0 × 10⁻³ and 6.0 × 10⁻⁴ μM was significantly inhibited by antioxidants, catalase and vitamin C. In conclusion, the present study demonstrated, through the direct and real-time measurement of respiratory function in mitochondria, that a marked inhibition of mitochondrial ETS function in cardiomyocytes was induced by T-2 toxin and DON and that the mitochondrial dysfunction by T-2 toxin was largely associated with oxidative stress.
本研究通过测量耗氧量（OCR），研究了两种代表性的单端孢霉烯族真菌毒素 T-2 毒素和脱氧雪腐镰刀菌烯醇（DON）对大鼠心肌细胞线粒体电子传递系统（ETS）的体外影响。通过“线粒体应激试验”量化了 ATP 连接的 OCR 和线粒体 ETS 的储备能力（RC），该试验通过 OCR 对寡霉素和羰基氰化物-p-三氟甲氧基苯腙的反应来估计，使用细胞外通量分析仪。T-2 毒素在 6×10⁻¹至 6×10⁻⁵ μM 的浓度下，DON 在 0.78 至 100 μM 的浓度下作用 24 小时，显著抑制了基础 OCR。估计心肌细胞毒性的阈值为 6.0×10⁻⁶至 6.0×10⁻⁵ μM，对 T-2 毒素的 ATP 连接的 OCR 和 RC 均有毒性，对 ATP 连接的 OCR 的毒性阈值为 0.39 至 0.78 μM，对 RC 的毒性阈值为 1.56 至 3.13 μM。浓度为 6.0×10⁻³和 6.0×10⁻⁴ μM 的 T-2 毒素暴露的心肌细胞 OCR 下降被抗氧化剂、过氧化氢酶和维生素 C 显著抑制。总之，本研究通过直接和实时测量线粒体呼吸功能，表明 T-2 毒素和 DON 显著抑制心肌细胞线粒体 ETS 功能，并且 T-2 毒素引起的线粒体功能障碍主要与氧化应激有关。
