Peroxidative Stress in Diabetic Blood Vessels: Reversal by Pancreatic Islet Transplantation

Abstract

Diabetic complications are believed to arise, in part, through an increase in oxidative stress. We characterized antioxidant status in vascular tissue in untreated diabetic rats and in diabetic rats rendered euglycemic by pancreatic islet transplantation. Three key endogenous antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) were measured. Sprague-Dawley rats with streptozotocin-induced diabetes were killed after 8 weeks of untreated hyperglycemia and compared with age-matched controls. Eight weeks of untreated diabetes resulted in a significant increase of tissue catalase in aorta, iliac artery, and femoral artery as compared with controls. No significant changes in either superoxide dismutase or glutathione peroxidase were observed in aorta, iliac artery, or femoral artery of diabetic animals. This increase in catalase in diabetic vascular tissue suggests increased oxidative stress due to chronic exposure to H2O2 in vivo. To assess the impact of islet transplantation on oxidative stress in vascular tissue, inbred Lewis strain rats were rendered diabetic with streptozotocin. After 8 weeks of untreated diabetes, rats received an intraportal islet isograft and were monitored for 4 subsequent weeks of euglycemia. Islet transplantation improved weight gain and normalized blood glucose and total glycosylated hemoglobin. While catalase was significantly increased in aorta and iliac artery at 8 and 12 weeks of diabetes, vascular catalase was restored to normal by islet transplantation. These data suggest that islet transplantation is an effective treatment strategy to minimize increased oxidative stress in diabetic vasculature.

Impairment of nitric oxide-mediated relaxations in anaesthetized autoperfused streptozotocin-induced diabetic rats

“…Glycosylated proteins (Angulo et al 1996;Giugliano et al 1996) or receptor-mediated mechanisms Wautier et al 1996) seem to be a main source of free radicals in diabetes. Superoxide anion production appears to be directly related to glycaemic control, both in diabetic patients (Ceriello et al 1991) and streptozotocin-induced diabetic rats (Pieper et al 1995b). …”

“…Indeed, some previous studies suggest that the oxidative stress observed in diabetic animals and patients is directly related to the metabolic control of the disease (Ceriello et al 1991;Pieper et al 1995b). Superoxide anion, hydroxyl radical, and hydrogen peroxide are likely to be involved in diabetic endothelial dysfunction, the role of superoxide anions being clearly established, as superoxide dismutase (SOD) is able to recover endothelium-dependent relaxations (Hattori et al 1991;Pieper et al 1992;Chang et al 1993).…”

Loss of adaptation to oxidative stress as a mechanism for aortic damage in aging rats

“…Catalase activity was assayed by H 2 O 2 consumption, following Aebi's method (3) modified by PIEPER et al (33). Ethanol was added (1:100 v/v) to the supernatants and incubated for 30 min in an ice bath.…”

Sodium tungstate alleviates biomechanical properties of diabetic rat femur via modulation of oxidative stress

“…Despite the contradictory results that present decreased or unchanged SOD activities (Pieper et al 1995;Liang et al 2011), the lack of significant difference can be attributed to the greater rate constant of SOD for dismutation of superoxide radical to form H 2 O 2 than the subsequent reaction which degrades H 2 O 2 (Pieper et al 1995). Moreover the tissue used for assessment of oxidative stress can be the reason of these differences in enzymes' activity.…”

“…Under normal conditions, H 2 O 2 is derived by dismutation of superoxide radical and detoxified by either CAT and/or GPx. At low concentration of H 2 O 2 GPx is the predominant pathway whereas catalase appears to be the preferred pathway for detoxification at higher amounts of H 2 O 2 (Pieper et al 1995;Baud et al 2004). This is due probably to extremely high Km of CAT than the Km of GPx which means CAT is particularly important when the clearance of H 2 O 2 in high concentrations is required (Baud et al 2004).…”