Hexavalent chromium induces mitochondrial dynamics disorder in rat liver by inhibiting AMPK/PGC-1α signaling pathway

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 gamma coactivator 1 alpha (PGC-1 alpha) 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-1 alpha signaling pathway in rat liver. (C) 2020 Elsevier Ltd. All rights reserved.