Diabetes and mitochondrial oxidative stress: a study using heart mitochondria from the diabetic Goto-Kakizaki rat.
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 determining alpha-tocopherol, GSH and coenzyme Q content. Although no difference of alpha-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.
Santos
Dario Loureiro
DL
University of Trás-os-Montes e Alto Douro, Vila Real, Portugal.
Palmeira
Carlos Marques
CM
Seiça
Raquel
R
Dias
José
J
Mesquita
José
J
Moreno
António Joaquim
AJ
Santos
Maria Sancha
MS
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008297:Male; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000648:ultrastructure; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D014451:Ubiquinone; D005978:Glutathione