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

Meifeng Xu, Muhammad Ashraf

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)75-79
Number of pages5
JournalJournal of molecular and cellular cardiology
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Mitochondrial Membrane Potential
Melatonin
Doxorubicin
Muscle Cells
Wounds and Injuries
L-Lactate Dehydrogenase
Reactive Oxygen Species
Mitochondria
Iodides
Staining and Labeling

Keywords

  • Doxorubicin
  • Melatonin
  • Mitochondrial Membrane Potential
  • Myocyte

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

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abstract = "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.",
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author = "Meifeng Xu and Muhammad Ashraf",
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N2 - 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.

AB - 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.

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