Jiangsu Agri-animal Husbandry Vocational College, Taizhou, 225300, Jiangsu Province, China.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.
Food Chem Toxicol. 2024 Sep;191:114877. doi: 10.1016/j.fct.2024.114877. Epub 2024 Jul 23.
Ochratoxin A (OTA) induces kidney damage in animals and humans. Ferroptosis is an iron-dependent form of regulated cell death that is involved in OTA-induced kidney injury. Quercetin (QCT), which is commonly found in numerous fruit and vegetables, has extensive pharmacological properties, such as anti-oxidant and anti-inflammatory. The present study aimed to evaluate the effects of QCT on OTA-induced kidney damage and the associated ferroptosis mechanism in mice. The results showed that OTA induced kidney damage, as demonstrated by the presence of kidney histopathological lesions, increased serum BUN and CRE levels, mRNA levels of Ntn1, Kim1, Tnfa, Ilb and Il6, and immunofluorescence of TNFα. OTA induced lipid peroxidation and ferroptosis by increasing the MDA level, 4-HNE production, and the iron concentration, decreasing the GSH content, increasing ACSL4 and HO-1 mRNA and protein levels, and decreasing GPX4 mRNA and protein levels. QCT supplementation alleviated OTA-induced kidney damage and inhibited OTA-induced lipid peroxidation and ferroptosis by reversing the OTA-induced above changes. Erastin weakened the protective effects of QCT on the histopathological damage, renal function, and inflammation induced by OTA. These findings indicated that QCT alleviated OTA-induced kidney injury through ferroptosis, suggesting that QCT might serve as a feed additive in mycotoxin contamination environments.
赭曲霉毒素 A（OTA）可诱导动物和人体的肾脏损伤。铁死亡是一种铁依赖性的细胞程序性死亡形式，参与 OTA 诱导的肾脏损伤。槲皮素（QCT）广泛存在于许多水果和蔬菜中，具有广泛的药理学特性，如抗氧化和抗炎作用。本研究旨在评估 QCT 对 OTA 诱导的小鼠肾脏损伤和相关铁死亡机制的影响。结果表明，OTA 可诱导肾脏损伤，表现为肾脏组织病理学损伤、血清 BUN 和 CRE 水平升高、Ntn1、Kim1、Tnfa、Ilb 和 Il6 的 mRNA 水平以及 TNFα的免疫荧光。OTA 通过增加 MDA 水平、4-HNE 产生和铁浓度，降低 GSH 含量，增加 ACSL4 和 HO-1mRNA 和蛋白水平，降低 GPX4 mRNA 和蛋白水平，诱导脂质过氧化和铁死亡。QCT 补充可通过逆转 OTA 引起的上述变化来缓解 OTA 诱导的肾脏损伤并抑制 OTA 诱导的脂质过氧化和铁死亡。恩替诺特削弱了 QCT 对 OTA 引起的组织病理学损伤、肾功能和炎症的保护作用。这些发现表明，QCT 通过铁死亡缓解 OTA 诱导的肾脏损伤，提示 QCT 可能在霉菌毒素污染环境中作为饲料添加剂使用。
