Melatonin protects against chromium(VI)-induced cardiac injury via activating the AMPK/Nrf2 pathway.


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. Electronic address: [Email]


Chromium (Cr) threatens health by causing oxidative stress. However, effective therapy for cardiac damage mediated by potassium dichromate (K2Cr2O7) still has not been defined. Melatonin (MT) possesses a number of biological activities. Our study was performed to explore the effect and mechanism of MT on Cr(VI)-induced cardiac damage by conducting both in vitro and in vivo studies. Twenty eight male Wistar rats were randomly assigned to four groups: control, MT (20 mg/kg subcutaneously), K2Cr2O7 (4 mg/kg intraperitoneally), and K2Cr2O7 + MT. We measured biomarkers of oxidative stress and cardiac function, and performed histopathological analysis, assay of terminal deoxynucleotidyl transferase-mediated deoxyuracil nucleoside triphosphate nick end labeling and protein levels, and the viability assay of cultured cardiomyocytes in vitro. Our results showed that MT ameliorated K2Cr2O7-induced oxidative stress, apoptosis, and the release of inflammatory mediators in the rat heart. MT also promoted adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, upregulated expression of proteins that nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, and nicotinamide adenine dinucleotide phosphatase: quinone-acceptor 1, and inhibited nuclear factor kappa B in the heart of rats exposed to K2Cr2O7. Furthermore, MT increased B-cell lymphoma gene 2 (Bcl-2) and B-cell lymphoma extra large protein levels and decreased cleaved caspase 3, P53, and Bcl-2-associated X protein levels. Furthermore, the experiment in vitro showed that MT increased the cells viability and protein levels of Nrf2 and phosphorylated-AMPK in H9C2 cells treated with K2Cr2O7. Collectively, our results demonstrate that MT protects against Cr-induced cardiac damage via activating the AMPK/Nrf2 pathway.


AMPK/Nrf2,Cardiac injury,Melatonin chromium(VI),NF-κB,Oxidative stress,