大黄素
氧化应激
谷胱甘肽
化学
活性氧
超氧化物歧化酶
谷胱甘肽过氧化物酶
药理学
肾毒性
脂质过氧化
生物化学
毒性
丙二醛
抗氧化剂
生物
酶
有机化学
作者
Miao Xing,Xiaoyu Ma,Xi Wang,Haoze Wang,Minjuan Xie,Ziwen Zhang,Jie Zhou
摘要
Abstract Emodin has been demonstrated to possess multiple pharmacological activities. However, emodin has also been reported to induce nephrotoxicity at high doses and with long‐term use, and the underlying mechanism has not been fully disclosed. The current study aimed to investigate the roles of oxidative stress and ferroptosis in emodin‐induced kidney toxicity. Mice were intraperitoneally treated with emodin, and NRK‐52E cells were exposed to emodin in the presence or absence of treatment with Jagged1, SC79, or t‐BHQ. Emodin significantly upregulated the levels of blood urea nitrogen, serum creatinine, malondialdehyde, and Fe 2+ , reduced the levels of superoxide dismutase and glutathione, and induced pathological changes in the kidneys in vivo. Moreover, the viability of NRK‐52E cells treated with emodin was reduced, and emodin induced iron accumulation, excessive reactive oxygen species production, and lipid peroxidation and depolarized the mitochondrial membrane potential ( ΔΨm ). In addition, emodin treatment downregulated the activity of neurogenic locus notch homolog protein 1 (Notch1), reduced the nuclear translocation of nuclear factor erythroid‐2 related factor 2 (Nrf2), and decreased glutathione peroxidase 4 protein levels. However, Notch1 activation by Jagged1 pretreatment, Akt activation by SC79 pretreatment, or Nrf2 activation by t‐BHQ pretreatment attenuated the toxic effects of emodin in NRK‐52E cells. Taken together, these results revealed that emodin‐induced ferroptosis triggered kidney toxicity through inhibition of the Notch1/Nrf2/glutathione peroxidase 4 axis.
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