College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 600 Changjiang Road, Harbin, 150030, China.
College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, China.
Environ Pollut. 2020 Oct;265(Pt A):114855. doi: 10.1016/j.envpol.2020.114855. Epub 2020 May 23.
Occupational exposure to hexavalent chromium (Cr(VI)) can cause cytotoxicity and carcinogenicity. In this study, we established a liver injury model in rats via intraperitoneal injection of potassium dichromate (0, 2, 4, and 6 mg/kg body weight) for 35 d to investigate the mechanism of Cr(VI)-induced liver injury. We found that Cr(VI) induced hepatic histopathological lesions, oxidative stress, and apoptosis and reduced the expression of mitochondrial-related regulatory factors such as adenosine 5'-monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in a dose-dependent manner. Furthermore, Cr(VI) promoted mitochondrial division and inhibited fusion, leading to increased expression of caspase-3 and production of mitochondrial reactive oxygen species. Our study demonstrates that long-term exposure to Cr(VI) induces mitochondrial dynamics disorder by inhibiting AMPK/PGC-1α signaling pathway in rat liver.
职业性接触六价铬（Cr(VI)）会导致细胞毒性和致癌性。在这项研究中，我们通过腹腔注射重铬酸钾（0、2、4 和 6mg/kg 体重）建立了大鼠肝损伤模型，以研究 Cr(VI)诱导肝损伤的机制。我们发现 Cr(VI)诱导肝组织病理学损伤、氧化应激和细胞凋亡，并呈剂量依赖性降低线粒体相关调节因子如腺苷 5'-单磷酸激活蛋白激酶（AMPK）和过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）的表达。此外，Cr(VI)促进线粒体分裂并抑制融合，导致 caspase-3 表达增加和线粒体活性氧的产生。我们的研究表明，长期暴露于 Cr(VI)会通过抑制 AMPK/PGC-1α 信号通路诱导大鼠肝脏中线粒体动力学紊乱。
