Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, PR China.
Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of Animal Common Disease Prevention, Northeast Agricultural University, Harbin, 150030, PR China.
Food Chem Toxicol. 2018 Jan;111:27-43. doi: 10.1016/j.fct.2017.10.057. Epub 2017 Nov 7.
Deoxynivalenol (DON), zearalenone (ZEN) and fumonisin B (FB) are among the most toxicologically important Fusarium toxins commonly found in nature that lead to nephrotoxicity in animals. The present study investigated that the individual and combined effects of subcytotoxic DON (0.25 μM), ZEN (20 μM) and FB (10 μM) on oxidative stress and apoptosis in porcine kidney cells (PK15). In addition, the protective effect of N-acetylcysteine (NAC) against the toxicity of Fusarium toxins was also evaluated. Our results showed that the activities of glutathione reductase (GR) and total superoxide dismutase (SOD) were affected by DON, ZEN and FB, and this change in activity induced reactive oxygen species (ROS) and malondialdehyde (MDA) production, increased apoptosis and regulated the mRNA expression of Bax, Bcl-2, caspase-3, caspase-9, cytochrome c (cyto c) and P53. This study demonstrated the complexity of combined mycotoxin infection since the combination of toxins exhibited more profound defects in the oxidative stress responses and apoptosis. Moreover, NAC reduced the oxidative damage and inhibited the apoptosis induced by Fusarium toxins. It was concluded that oxidative damage and apoptosis through the mitochondria-dependent channel were the mechanisms of Fusarium toxin mediated toxicity, and NAC reversed these damages to some extent.
脱氧雪腐镰刀菌烯醇（DON）、玉米赤霉烯酮（ZEN）和伏马菌素 B（FB）是自然界中最具毒理学意义的镰刀菌毒素之一，可导致动物的肾毒性。本研究探讨了亚细胞毒性 DON（0.25μM）、ZEN（20μM）和 FB（10μM）对猪肾细胞（PK15）氧化应激和细胞凋亡的单独和联合作用。此外，还评估了 N-乙酰半胱氨酸（NAC）对镰刀菌毒素毒性的保护作用。结果表明，DON、ZEN 和 FB 影响谷胱甘肽还原酶（GR）和总超氧化物歧化酶（SOD）的活性，这种活性变化诱导活性氧（ROS）和丙二醛（MDA）的产生，增加细胞凋亡并调节 Bax、Bcl-2、caspase-3、caspase-9、细胞色素 c（cyto c）和 P53 的 mRNA 表达。本研究表明，由于毒素的组合表现出更严重的氧化应激反应和细胞凋亡缺陷，因此联合霉菌毒素感染的情况较为复杂。此外，NAC 降低了由镰刀菌毒素引起的氧化损伤并抑制了细胞凋亡。结论是，通过线粒体依赖性通道的氧化损伤和细胞凋亡是镰刀菌毒素介导毒性的机制，NAC 在某种程度上逆转了这些损伤。
