Melatonin protects against chromium(VI)-induced cardiac injury via activating the AMPK/Nrf2 pathway
| Autor: | Xiangyu Ma, Xinyue Xu, Lanjie Yu, Zhigang Zhang, Xiaoyan Zheng, Jiayi Li, Qingjie Lv, Yu Du, Hongxing Sun, Yuan Wu, Xuerui Li |
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| Rok vydání: | 2019 |
| Předmět: |
Chromium
Male Cardiotonic Agents Heart Diseases NF-E2-Related Factor 2 Phosphatase Caspase 3 AMP-Activated Protein Kinases 010402 general chemistry medicine.disease_cause 01 natural sciences Biochemistry Inorganic Chemistry medicine Animals Viability assay Rats Wistar Protein kinase A Melatonin 010405 organic chemistry Chemistry AMPK Molecular biology Adenosine Rats 0104 chemical sciences Apoptosis Potassium Dichromate Oxidative stress Signal Transduction medicine.drug |
| Zdroj: | Journal of Inorganic Biochemistry. 197:110698 |
| ISSN: | 0162-0134 |
| DOI: | 10.1016/j.jinorgbio.2019.110698 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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