Chronic melatonin treatment prevents age-dependent cardiac mitochondrial dysfunction in senescence-accelerated mice.
Heart mitochondria from female senescence-accelerated (SAMP8) and senescence-resistant (SAMR1) mice of 5 or 10 months of age, were studied. Mitochondrial oxidative stress was determined by measuring the levels of lipid peroxidation, glutathione and glutathione disulfide and glutathione peroxidase and reductase activities. Mitochondrial function was assessed by measuring the activity of the respiratory chain complexes and ATP content. The results show that the age-dependent mitochondrial oxidative damage in the heart of SAMP8 mice was accompanied by a reduction in the electron transport chain complex activities and in ATP levels. Chronic melatonin administration between 1 and 10 months of age normalized the redox and the bioenergetic status of the mitochondria and increased ATP levels. The results support the presence of significant mitochondrial oxidative stress in SAM mice at 10 months of age, and they suggest a beneficial effect of chronic pharmacological intervention with melatonin, which reduces the deteriorative and functional oxidative changes in cardiac mitochondria with age.
Rodríguez
María I
MI
Departamento de Fisiología, Instituto de Biotecnología, Universidad de Granada, Granada, Spain.
Carretero
Miguel
M
Escames
Germaine
G
López
Luis C
LC
Maldonado
María D
MD
Tan
Dun-Xian
DX
Reiter
Russel J
RJ
Acuña-Castroviejo
Darío
D
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D045222:Electron Transport Chain Complex Proteins / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D019803:Glutathione Disulfide / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
D000975:Antioxidants; D045222:Electron Transport Chain Complex Proteins; D000255:Adenosine Triphosphate; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; D008550:Melatonin; D019803:Glutathione Disulfide