Exploring the kidney hazard of exposure to mercuric chloride in mice:Disorder of mitochondrial dynamics induces oxidative stress and results in apoptosis. (November 2019)

• Record Type: Journal Article
• Authors: Li, Siyu; Baiyun, Ruiqi; Lv, Zhanjun; Li, Jiayi; Han, Dongxu; Zhao, Wenyue; Yu, Lanjie; Deng, Ning; Liu, Zhiyan; Zhang, Zhigang
• Is Part Of: Chemosphere. Volume 234(2019)
• Page Start: 822
• Page End: 829
• Publication Date: 2019-11
• Subjects: HgCl2 -- Mitochondrial dynamics -- Kidney hazard -- Nrf2 -- Sirt1/PGC-1α -- Apoptosis; Bax Bcl-2-associated X protein -- Bcl-2 B-cell lymphoma gene 2 -- BUN blood urea nitrogen -- CREA serum creatinine -- Drp1 dynamin-related protein 1 -- HgCl2 mercuric chloride -- H&E hematoxylin and eosin -- HO-1 heme oxygenase-1 -- GSH reduced glutathione -- MDA malondialdehyde -- Mfn2 mitofusin 2 -- NQO1 nicotinamide adenine dinucleotide phosphatase: quinoneacceptor 1 -- Nrf2 nuclear factor erythroid 2-related factor 2 -- PBS phosphate-buffered saline -- PGC-1α peroxisome proliferator-activated receptor-γ coactivator-1α -- ROS reactive oxygen species -- Sirt1 silent information regulator two ortholog 1 -- SOD2 manganese superoxide dismutase 2 -- TEM transmission electron microscope -- TUNEL terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2019.06.096
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Mercury is one of the 10 toxic chemicals with major public health concerns. Continuous exposure to low levels of heavy metals including mercury is related to renal injury, especially in children. This study investigated the possible molecular mechanism of inorganic mercury-induced kidney injury. Twenty eight Kunming mice were divided into four groups (n = 7), and treated with 0, 20, 40, 80 mg/L mercuric chloride (HgCl2 ) in drinking water for 16 weeks respectively. All the HgCl2 exposure mice displayed different degrees of renal injury, which was diagnosed by hematoxylin and eosin stain, biochemical analysis, and ultrastructure examination. The treatment of HgCl2 inhibited the silent information regulator two ortholog 1 (Sirt1)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) signaling pathway and resulted the disorder of mitochondrial dynamics, as evidenced by the increasing expression of dynamin-related protein 1 and decreasing expression of mitofusin 2. Meanwhile, HgCl2 inhibited the nuclear factor erythroid 2-related factor 2 (Nrf2) axis. The abnormality of mitochondrial dynamics and the suppression of Nrf2 axis exacerbated oxidative stress, and then induced cell apoptosis. These findings demonstrated that the disorder of mitochondrial dynamics induced by HgCl2 activated oxidative stress, and further resulted in renal apoptosis through inhibiting the Sirt1/PGC-1α signaling pathway and the Nrf2 axis. Graphical abstract: The disorder of mitochondrial dynamics induced by HgCl2 activated oxidative stress and furtherly resulted in renal apoptosis through inhibiting the Sirt1/PGC-1α signaling pathway and the Nrf2 axis. Image 10646807 Highlights: Continuous and low levels of HgCl2 exposure induced kidney injury. The disorder of mitochondrial dynamics is a key of HgCl2 -induced kidney injury. The disorder of mitochondrial dynamics is induced by Sirt1/PGC-1α inhibition. HgCl2 activated oxidative stress via inhibiting Nrf2 axis. The disorder of mitochondrial dynamics resulted in renal apoptosis.