Melatonin protection against lethal myocyte injury induced by doxorubicin as reflected by effects on mitochondrial membrane potential

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 (Deltapsi(m)) prior to severe cell injury. Myocytes were incubated with 20 mumol/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 Deltapsi(m). Pretreatment with melatonin (1 mmol/l) for one hour prevented the release of LDH and restored Deltapsi(m). The data support the hypothesis that DOX induces damage to mitochondria through radicals, and this is reflected in depolarization of Deltapsi(m) which was prevented by melatonin. (C) 2002 Elsevier Science Ltd.