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Diabetes and mitochondrial oxidative stress: A study using heart mitochondria from the diabetic Goto-Kakizaki rat

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Abstract

Increasing evidence shows that the overproduction of reactive oxygen species, induced by diabetic hyperglycemia, contributes to the development of several cardiopathologies. The susceptibility of diabetic hearts to oxidative stress, induced in vitro by ADP-Fe2+ in mitochondria, was studied in 12-month-old Goto-Kakizaki rats, a model of non-insulin dependent diabetes mellitus, and normal (non-diabetic) Wistar rats. In terms of lipid peroxidation the oxidative damage was evaluated on heart mitochondria by measuring both the O2 consumption and the concentrations of thiobarbituric acid reactive substances. Diabetic rats display a more intense formation of thiobarbituric acid reactive substances and a higher O2 consumption than non-diabetic rats. The oxidative damage, assessed by electron microscopy, was followed by an extensive effect on the volume of diabetic heart mitochondria, as compared with control heart mitochondria. An increase in the susceptibility of diabetic heart mitochondria to oxidative stress can be explained by reduced levels of endogenous antioxidants, so we proceeded in determinating α-tocopherol, GSH and coenzyme Q content. Although no difference of α-tocopherol levels was found in diabetic rats as compared with control rat mitochondria, a significant reduction in GSH (21.5% reduction in diabetic rats) and coenzyme Q levels of diabetic rats was observed. The data suggest that a significant decrease of coenzyme Q9, a potent antioxidant involved in the elimination of mitochondria-generated reactive oxygen species, may be responsible for an increased susceptibility of diabetic heart mitochondria to oxidative damage.

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Authors and Affiliations

  1. University of Tr%aacute;s-os-Montes e Alto Douro, Vila Real, Portugal

    Dario Loureiro Santos

  2. Center for Neurosciences and Cell Biology of Coimbra and Department of Zoology, University of Coimbra, Coimbra, Portugal

    Carlos Marques Palmeira & Antonio Joaquim Moreno

  3. Center for Neurosciences and Cell Biology of Coimbra and Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Raquel Sei%ccedil;a

  4. Department of Botany, University of Coimbra, Coimbra, Portugal

    José Dias & José Mesquita

  5. Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology, University of Coimbra, 3004-517, Coimbra, Portugal

    Maria Sancha Santos

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  1. Dario Loureiro Santos
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  2. Carlos Marques Palmeira
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Santos, D.L., Palmeira, C.M., Sei%ccedil;a, R. et al. Diabetes and mitochondrial oxidative stress: A study using heart mitochondria from the diabetic Goto-Kakizaki rat. Mol Cell Biochem 246, 163–170 (2003). https://doi.org/10.1023/A:1023475022025

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