Abstract：
Patulin (PAT), the most common mycotoxin, is widespread in foods and beverages which poses a serious food safety issue to human health. Our previous research confirmed that exposure to PAT can lead to acute kidney injury (AKI). Curcumin is the most abundant active ingredient in turmeric rhizome with various biological activities. The aim of this study is to investigate whether curcumin can prevent the renal injury caused by PAT, and to explore potential mechanisms. In vivo, supplementation with curcumin attenuated PAT-induced ferroptosis. Mechanically, curcumin inhibited autophagy, led to the accumulation of p62 and its interaction with Keap1, promoted the nuclear translocation of nuclear factor E2 related factor 2 (Nrf2), and increased the expression of antioxidant stress factors in the process of ferroptosis. These results have also been confirmed in HKC cell experiments. Furthermore, knockdown of Nrf2 in HKC cells abrogated the protective effect of curcumin on ferroptosis. In conclusion, we confirmed that curcumin mitigated PAT-induced AKI by inhibiting ferroptosis via activation of the p62/Keap1/Nrf2 pathway. This study provides new potential targets and ideas for the prevention and treatment of PAT.
摘要：
Patulin(PAT),最常见的霉菌毒素，在食品和饮料中普遍存在，这对人类健康构成了严重的食品安全问题。我们先前的研究证实，暴露于PAT可导致急性肾损伤（AKI）。姜黄素是姜黄根茎中最丰富的活性成分，具有多种生物活性。这项研究的目的是探讨姜黄素是否可以预防PAT引起的肾损伤。探索潜在的机制。在体内,补充姜黄素减弱PAT诱导的铁细胞凋亡。机械上,姜黄素抑制自噬，导致p62的积累及其与Keap1的相互作用，促进核因子E2相关因子2（Nrf2）的核易位，并增加了铁凋亡过程中抗氧化应激因子的表达。这些结果也已在HKC细胞实验中得到证实。此外，HKC细胞中Nrf2的敲除消除了姜黄素对铁凋亡的保护作用。总之,我们证实姜黄素通过激活p62/Keap1/Nrf2途径抑制铁凋亡,从而减轻PAT诱导的AKI.本研究为PAT的防治提供了新的潜在靶点和思路。
