氧化应激
肾毒性
线粒体
SIRT3
KEAP1型
肾
线粒体毒性
MFN2型
TFAM公司
化学
生物
细胞生物学
药理学
线粒体融合
生物化学
内分泌学
线粒体生物发生
转录因子
线粒体DNA
锡尔图因
乙酰化
基因
作者
Jing Ge,Cong Zhang,Yanchun Sun,Qi Zhang,Mei‐Wei Lv,Kai Guo,Jin‐Long Li
标识
DOI:10.1016/j.scitotenv.2019.06.405
摘要
Cadmium (Cd) is a widespread environmental pollutant that accumulates in living systems and represents a significant global health hazard. Cd poses a toxicity threat to both human and animal health, including that of birds. Further knowledge of Cd toxicology pathways will allow for a better understanding of Cd-induced nephrotoxicity. To evaluate Cd-induced nephrotoxicity through potential oxidative damage, male chickens were treated with 0 mg/kg, 35 mg/kg or 70 mg/kg CdCl2 in diet for 90 days. Markedly, histopathology indicated renal tubular epithelial cell swelling, renal function CREA content abnormalities, biochemical and morphologic indices indicative of Cd-induced kidney injury. Cd toxicity induced the up-regulation of Nrf2 and downstream target genes that relieve oxidative stress. Meanwhile, Cd disrupted the homeostasis of trace elements and promoted oxidative damage. Cd interfered with mitochondrial unfolded protein response (UPRmt)-related factors (SIRT1, SIRT3, PGC-1α, TFAM, Nrf1, and HTRA2) and disrupted the homeostasis of mitochondrial dynamics (OPA1, MFN1, MFN2, Fis1 and MFF), thereby exacerbating mitochondrial structural damage and mitochondrial dysfunction. In conclusion, our study demonstrated that the nephrotoxicity of Cd exposure results in oxidative stress and mitochondrial dysfunction by activating the Nrf2 signaling pathway and inhibiting UPRmt in the kidneys.
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