Melatonin Prevents Mitochondrial Damage Induced by Doxorubicin in Mouse Fibroblasts Through Ampk-Ppar Gamma-Dependent Mechanisms
| Autor: | Eylem Taskin, Celal Güven, Handan Akçakaya |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Programmed cell death Cell Survival Caspase 3 Apoptosis Mitochondrion Biology Pharmacology AMP-Activated Protein Kinases medicine.disease_cause Antioxidants Melatonin 03 medical and health sciences Mice 0302 clinical medicine medicine polycyclic compounds Animals Doxorubicin Drug Interactions Membrane Potential Mitochondrial Animal Study AMPK Cytochromes c General Medicine Fibroblasts Mitochondria PPAR gamma Oxidative Stress 030104 developmental biology 030220 oncology & carcinogenesis NIH 3T3 Cells Oxidative stress medicine.drug |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 1234-1010 |
| Popis: | BACKGROUND Doxorubicin (brand name: Adriamycin®) is used to treat solid tissue cancer but it also affects noncancerous tissues. Its mechanism of cytotoxicity is probably related to increased oxidation, mitochondrial dysfunction, and apoptosis. Melatonin is reported to have antiapoptotic and antioxidative effects. The aim of this study was to determine whether melatonin would counteract in vitro cytotoxicity of doxorubicin in mouse fibroblasts and determine the pathway of its action against doxorubicin-induced apoptosis. MATERIAL AND METHODS We measured markers of apoptosis (cytochrome-c, mitochondrial membrane potential, and apoptotic cell number) and oxidative stress (total oxidant and antioxidant status) and calculated oxidant stress index in 4 groups of fibroblasts: controls, melatonin-treated, doxorubicin-treated, and fibroblasts concomittantly treated with a combination of melatonin and doxorubicin. RESULTS Melatonin given with doxorubicin succesfully countered apoptosis generated by doxorubicin alone, which points to its potential as a protective agent against cell death in doxorubicin chemotherapy. This also implies that patients should be receiving doxorubicin treatment when their physiological level of melatonin is at its highest, which is early in the morning. CONCLUSIONS This physiological level may not be high enough to overcome doxorubicin-induced oxidative stress, but adjuvant melatonin treatment may improve quality of life. Further research is needed to verify our findings. |
| Databáze: | OpenAIRE |
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