College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, 712100, China.
College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Chem Biol Interact. 2022 Mar 1;355:109850. doi: 10.1016/j.cbi.2022.109850. Epub 2022 Feb 9.
3-Chloro-1, 2-propanediol (3-MCPD) is a widespread food contaminant with kidney as the main target organ. The exploration of ingredients as intervention strategy towards 3-MCPD induced nephrotoxicity is needed. Diosgenin (DIO) is a steroidal saponin presented in several plants and foods. Here we assessed whether DIO attenuates nephrotoxicity induced by 3-MCPD using Human embryonic kidney 293 (HEK293) cells and Sprague-Dawley (SD) rats. The results showed that DIO (2, 6, 8 μM) increased cell viability and exerted inhibitory effect on caspase 3 and caspase 9 activities. Histological examination of rats showed that 15 mg/kg bw DIO ameliorated renal pathological changes caused by 3-MCPD (30 mg/kg bw). DIO also induced autophagy and the blockade of autophagy with 3-Methyladenine (3-MA) aggravated mitochondrial apoptosis induced by 3-MCPD in HEK293 cells. Moreover, treatment with DIO caused an increase in p-LKB1/LKB1 and p-AMPK/AMPK expressions and a decrease in p-mTOR/mTOR, p-ULK1(Ser), p-P70S6K and p-4EBP1 expressions. Additionally, DIO improved mitochondrial dynamics mainly through inhibiting the relocation of DRP1 on mitochondria and enhancing MFN1 and MFN2 expressions. In conclusion, our study demonstrated for the first time that DIO protected against kidney injury induced by 3-MCPD through the induction of autophagy via LKB1-AMPK-mTOR pathway and the improvement of mitochondrial fission and fusion.
3-氯-1,2-丙二醇（3-MCPD）是一种广泛存在的食品污染物，其主要靶器官为肾脏。因此，需要探索成分作为干预 3-MCPD 诱导肾毒性的策略。薯蓣皂苷元（DIO）是一种存在于多种植物和食物中的甾体皂苷。在这里，我们使用人胚肾 293（HEK293）细胞和 Sprague-Dawley（SD）大鼠评估了 DIO 是否可以减轻 3-MCPD 诱导的肾毒性。结果表明，DIO（2、6、8 μM）可提高细胞活力，并对 caspase 3 和 caspase 9 的活性具有抑制作用。大鼠的组织学检查表明，15 mg/kg bw DIO 可改善 3-MCPD（30 mg/kg bw）引起的肾脏病理变化。DIO 还诱导自噬，而用 3-甲基腺嘌呤（3-MA）阻断自噬会加重 3-MCPD 在 HEK293 细胞中诱导的线粒体凋亡。此外，DIO 处理会导致 p-LKB1/LKB1 和 p-AMPK/AMPK 表达增加，而 p-mTOR/mTOR、p-ULK1（Ser）、p-P70S6K 和 p-4EBP1 表达减少。此外，DIO 主要通过抑制 DRP1 在线粒体上的重定位和增强 MFN1 和 MFN2 的表达来改善线粒体动力学。总之，我们的研究首次表明，DIO 通过 LKB1-AMPK-mTOR 通路诱导自噬并改善线粒体分裂和融合，从而防止 3-MCPD 引起的肾脏损伤。
