Melatonin (MLT) is highly protective against cardiotoxicity caused by doxorubicin (DOX). DOX induces cardiac damage via production of reactive oxygen species. This study tests the hypothesis that oxygen radicals generated by DOX disrupt mitochondrial membrane potential (Δψm) prior to severe cell injury. Myocytes were incubated with 20 μmol/l DOX for 24 h. Myocyte damage was estimated by lactate dehydrogenase (LDH) release. Mitochondrial membrane potential was determined by staining myocytes with 5, 5′, 6, 6′-tetrachloro-1, 1′, 3, 3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1) using confocal microscope. A significant amount of LDH was observed after 24 h of treatment with DOX, Mitochondria in DOX-treated myocytes exhibited a collapse of Δπm. Pretreatment with melatonin (1 mmol/l) for one hour prevented the release of LDH and restored Δπm. The data support the hypothesis that DOX induces damage to mitochondria through radicals, and this is reflected in depolarization of Δπm, which was prevented by melatonin.
- Mitochondrial Membrane Potential
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine