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

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.