Protective Role of Superoxide Dismutase against Diabetogenic Drugs

Abstract

A B S T R A C T Copper-zinc superoxide dismutase (SOD) is present in relatively high concentrations in the ,-cells of human islets. The activity of the extracted enzyme is partially inhibited upon incubation with the diabetogenic drugs alloxan, streptozotocin, or Vacor. The role of this enzyme in protecting a-cells against chemically induced diabetes was further investigated.Incubation of intact canine islets with alloxan (0.2 mg/ml) and 4 mM glucose decreased the insulin secretory response by 87% during subsequent exposure to 28 mM glucose. Concomitantly the SOD-specific activity (units of enzyme activity per milligram immunoreactive SOD) decreased 50% in alloxan-exposed islets. When islets were protected from alloxan toxicity by including 28 mM glucose with alloxan, the insulin secretory response and SOD specific activity remained identical to controls. Thus, SOD specific activity correlates with maintenance of ,B-cell function.To test the effectiveness of SOD against streptozotocin in vitro, canine islets were incubated 10 min with or without streptozotocin (0.1 mg/ml) with 4 mM glucose; their functional integrity was tested subsequently as the insulin secretory response to 28 mM glucose. Exposure to streptozotocin alone decreased the response by 70%; inclusion of SOD (1.5 mg/ml) before and during exposure to streptozotocin completely prevented this effect. Cyanide-inactivated SOD was not effective.The potential of SOD to prevent streptozotocin-induced diabetes was tested in rats in vivo. SOD injected 10 s or 50 min before streptozotocin prevented or significantly attenuated diabetes. Injection of SOD and streptozotocin simultaneously was much less effective, and cyanide-inactivated SOP was ineffective. No protection was afforded by injection of SOD 12 or 24 h before streptozotocin.

Peroxiredoxin III protects pancreatic β cells from apoptosis

“…In vivo, over-expression of Cu/ZnSOD in diabetic animals provides protection against the development of alloxan-or STZ-induced diabetes. Moreover, addition of scavenging agents such as SOD, Catalase (Cat), guanidinoethyldisulphide, and metal chelators prior to alloxan, STZ, or cytokine exposure has prevented b cell death in isolated islets (Gandy et al 1982, Abdel-Rahman et al 1992, Suarez-Pinzon et al 2001. Lower concentrations of H 2 O 2 , however, seem to be involved in the regulation of physiological processes, e.g.…”

Suppression of KATP channel activity protects murine pancreatic β cells against oxidative stress

“…In vivo experiments show that transgenic mice with β cell-specific overexpression of Cu/Zn SOD are more resistant to alloxan-induced diabetes (11). Studies with rodents demonstrate that SOD administration can attenuate streptozotocin-induced (STZ-induced) hyperglycemia and diabetes (12)(13)(14). It was previously reported that antioxidant treatment exerts beneficial effects on β cell mass and insulin content in diabetic C57BL/KsJ-db/db mice (15).…”

Protective effect of Amomi semen extract on alloxan‐induced pancreatic β‐cell damage

“…Although the precise diabetogenic mechanism of alloxan is not fully understood, there is some evidence indicating that the tissue damage induced by alloxan is mediated through the formation of reactive oxygen species (ROS, Heikkila et al, 1976;Cohen and Heikkila, 1974;Kim et al, 1994;Park et al, 1995). There are many reports that the scavengers of ROS can ameliorate alloxan toxicity in vitro (Gandy et al, 1982;Abdel-Rahman et al, 1992) and in vivo (Grakvist et al, 1981;Heikkila and Cabbat, 1982). Okamoto (1985) proposed that the primary target of ROS produced from alloxan is the DNA of pancreatic β-cells.…”