Effect of diethyldithiocarbamate on diabetogenic action of alloxan in rats.

To determine whether alloxan action is mediated by hydroxyl radicals in vivo, we assayed methane sulfinic acid (MSA), a product of the trapping reaction of dimethyl sulfoxide (DMSO) with hydroxyl radicals. In DMSO-treated rats, the plasma levels of MSA were increased after injection of alloxan (75 mg/kg). This supports the hypothesis that the diabetogenic action of alloxan is mediated by hydroxyl radicals in vivo. The role of cytosolic superoxide dismutase (SOD) in protecting B cells against chemically induced diabetes was studied in rats injected intraperitoneally with diethyldithiocarbamate (DDC). When rats were injected intraperitoneally with DDC (750 mg/kg), the SOD activity at 2.5 h was decreased by 44% in the whole pancreas. The decreased SOD activity was affected by DDC but not by alloxan. Intraperitoneal injection of rats with DDC (750 mg/kg) increased diabetogenic susceptibility to a nondiabetogenic dose of alloxan (20 mg/kg). Subcutaneous injection of vitamin E, prior to administration of both DDC and alloxan, provided partial protection to the rats against the diabetogenic action. These findings suggest that the susceptibility to diabetogenic action of alloxan in B cells is augmented when the cellular SOD activity is inhibited. Thus, cellular SOD may play an important role in the maintenance of B cell function.