Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol.
The aim of this work was to study the mechanism of free radical formation in type 1 diabetes and its possible prevention. We have found oxidation of blood glutathione and an increase in plasma lipoperoxide levels in both human type 1 diabetes and experimental diabetes. Peroxide production by mitochondria does not increase in diabetes. On the contrary, the activity of xanthine oxidase, a superoxide-generating enzyme, increases in liver and plasma of diabetic animals. The increase in plasma xanthine oxidase activity may be explained by the increase in the hepatic release of this enzyme, which is not due to nonspecific membrane damage: release of other hepatic enzymes, such as the amino transferases, does not increase in diabetes. Superoxide formation by aortic rings of rabbits increases significantly in diabetes. This is completely inhibited by allopurinol, an inhibitor of xanthine oxidase. Heparin, which releases xanthine oxidase from the vessel wall, also decreases superoxide formation by aortic rings of diabetic animals. Treatment with allopurinol decreases oxidative stress in type 1 diabetic patients: hemoglobin glycation, glutathione oxidation, and the increase in lipid peroxidation are prevented. These results may have clinical significance in the prevention of late-onset vascular complications of diabetes.
Desco
Marí-Carmen
MC
Department of Physiology, Faculty of Medicine, University of Valencia, Valencia, Spain.
Asensi
Miguel
M
Márquez
Rafael
R
Martínez-Valls
José
J
Vento
Máximo
M
Pallardó
Federico V
FV
Sastre
Juan
J
Viña
José
J
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000201:enzymology; D004311:Double-Blind Method; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016166:Free Radical Scavengers; D005609:Free Radicals; D008315:Malondialdehyde; D000493:Allopurinol; D014969:Xanthine Oxidase; D005978:Glutathione; D019803:Glutathione Disulfide