Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
Chem Biol Interact. 2022 May 1;358:109884. doi: 10.1016/j.cbi.2022.109884. Epub 2022 Mar 15.
Aflatoxin B (AFB) is a toxic food pollutant that has extensive deleterious impacts on the kidney. Oxidative stress represents the primary mechanism of AFB nephrotoxicity and can also cause mitochondrial damage. Damaged mitochondria can trigger apoptosis leading to kidney injury. PINK1/Parkin-mediated mitophagy can alleviate mitochondrial injury to maintain cellular homeostasis, however, its role in AFB-induced kidney damage is unknown. To investigate the effect of PINK1/Parkin-mediated mitophagy on kidney impairment triggered by AFB, 40 male wild-type (WT) C57BL/6N mice were first assigned to 4 groups and orally exposed to AFB at 0, 0.5, 0.75, and 1 mg/kg body weight (BW) for 28 days. The results revealed that AFB induced kidney damage, oxidative stress, mitochondrial damage, apoptosis and activated PINK1/Parkin-mediated mitophagy with a dose-dependent effect. Then, 20 male WT C57BL/6N mice and 20 male Parkin knockout (Parkin) C57BL/6N mice were assigned to 4 groups and orally exposed to AFB at 0, 1, 0, and 1 mg/kg BW for 28 days. The results revealed that Parkin suppressed mitophagy and exacerbated kidney damage, oxidative stress, mitochondrial damage, and apoptosis under AFB exposure. The aforementioned evidences demonstrate that PINK1/Parkin-mediated mitophagy is activated by AFB and protects against kidney damage in mice.
黄曲霉毒素 B（AFB）是一种有毒的食物污染物，对肾脏有广泛的有害影响。氧化应激是 AFB 肾毒性的主要机制，也可导致线粒体损伤。受损的线粒体可以触发细胞凋亡，导致肾脏损伤。PINK1/Parkin 介导的线粒体自噬可以减轻线粒体损伤，维持细胞内稳态，然而，其在 AFB 诱导的肾脏损伤中的作用尚不清楚。为了研究 PINK1/Parkin 介导的线粒体自噬对 AFB 诱导的肾脏损伤的影响，首先将 40 只雄性野生型（WT）C57BL/6N 小鼠分为 4 组，分别口服暴露于 0、0.5、0.75 和 1 mg/kg 体重（BW）的 AFB 28 天。结果表明，AFB 诱导肾脏损伤、氧化应激、线粒体损伤、细胞凋亡，并呈剂量依赖性激活 PINK1/Parkin 介导的线粒体自噬。然后，将 20 只雄性 WT C57BL/6N 小鼠和 20 只雄性 Parkin 敲除（Parkin）C57BL/6N 小鼠分为 4 组，分别口服暴露于 0、1、0.5 和 1 mg/kg BW 的 AFB 28 天。结果表明，Parkin 抑制线粒体自噬，并在 AFB 暴露下加剧肾脏损伤、氧化应激、线粒体损伤和细胞凋亡。上述证据表明，PINK1/Parkin 介导的线粒体自噬被 AFB 激活，并在小鼠中保护肾脏免受损伤。
