Ochratoxin A (OTA) is a widespread food toxin produced by Aspergillus ochraceus and other molds. In this study, we developed and established acute OTA toxicity conditions in mice, which received daily oral doses of OTA between 0.5 up to 8 mg/kg body weight up to 7 days and were subjected to histological and biochemical analysis to characterize renal and hepatic damage. Oral administration of OTA for 7 days resulted in loss of body weight in a dose-dependent manner and increased the levels of serum biomarkers of hepatic and renal damage. The kidney was more sensitive to OTA-induced damage than the liver. In addition to necrosis, OTA induced hepatic and renal apoptosis in dose- and time-dependent manners. Especially, a high dose of OTA (8 mg/kg body weight) administered for 7 days led to necroptosis in both liver and kidney tissues. OTA dose-dependently increased the oxidative stress levels, including lipid peroxidation, in the liver and kidneys. OTA disrupted mitochondrial dynamics and structure in hepatic and renal cells, leading to the dysregulation of mitochondrial homeostasis. OTA increased transferrin receptor 1 and decreased glutathione peroxidase 4 levels in a dose- and time-dependent manner. These results suggest the induction of ferroptosis. Collectively, this study highlighted the characteristics of acute OTA-induced hepatic and renal toxicity in mice in terms of oxidative stress, mitochondrial damage, and multiple cell death mechanisms, including necroptosis and ferroptosis.

赭曲霉毒素 A (OTA) 是一种广泛存在的食物毒素，由赭曲霉和其他霉菌产生。在这项研究中，我们开发并建立了小鼠急性 OTA 毒性条件，小鼠每天口服 0.5 至 8 毫克/千克体重的 OTA，持续 7 天，并进行组织学和生化分析，以表征肾脏和肝脏损伤。口服OTA 7天会导致体重以剂量依赖性方式下降，并增加肝肾损伤的血清生物标志物水平。肾脏对 OTA 引起的损伤比肝脏更敏感。除了坏死之外，OTA还以剂量和时间依赖性方式诱导肝和肾细胞凋亡。特别是，连续7天施用高剂量OTA（8毫克/千克体重）会导致肝脏和肾脏组织坏死性凋亡。 OTA 剂量依赖性地增加肝脏和肾脏中的氧化应激水平，包括脂质过氧化。 OTA 破坏了肝细胞和肾细胞中的线粒体动力学和结构，导致线粒体稳态失调。 OTA 以剂量和时间依赖性方式增加转铁蛋白受体 1 并降低谷胱甘肽过氧化物酶 4 水平。这些结果表明铁死亡的诱导。总的来说，这项研究强调了 OTA 诱导的小鼠急性肝肾毒性的特征，包括氧化应激、线粒体损伤和多种细胞死亡机制，包括坏死性凋亡和铁死亡。