Protection against Alloxan-Induced Diabetes by Diethyldithiocarbamate and Disulfiram in Mice

Abstract

ABSTRACT-Diethyldithiocarbamate (DEDC, 0.25-2.00 mmol/kg) injected into mice at 0.5 hr prior to alloxan administration dose-dependently protected the mice against the diabetogenic actions of 75 mg/kg alloxan. Disulfiram (DS, 0.50-2.00 mmol/kg), a corresponding disulfide form, also exhibited similar pro tection. The maximum effect of DEDC was found by dosing at 0.5 hr prior to alloxan, and the effect afford ed by DEDC pretreatment persisted up to 3 hr, whereas the effect of DS was exhibited when the compound was given 0.5 hr prior to alloxan. Of the metabolites of DEDC, diethylamine and carbon disulfide had no effect. At 0.5 hr after injection, DEDC alone had a potent increasing ability on blood glucose in a dose dependent manner, but DS was less potent. Mannoheptulose, an antagonist of glucose action at pancreatic p-cells, when given 24 min after DEDC and 6 min before alloxan, eliminated the DEDC-induced protection. Fasted mice did not exhibit hyperglycemia at 0.5 hr after DEDC injection, and alloxan given at that time produced diabetes. These findings indicate that DEDC itself protected mice from alloxan-induced diabetes by the indirect mechanism of producing hyperglycemia at the time of alloxan administration. The anti diabetogenic action of low doses of DS and DEDC, in animals lacking hyperglycemia at the time of alloxan injection, is likely based on a mechanism other than one involving hyperglycemia.

The protective effect of ursodeoxycholic acid in alloxan‐induced diabetes

“…1 Antioxidants and metal chelators prevent alloxaninduced diabetes when injected together with or prior to alloxan treatment. 6,7 Treatment with antioxidants and scavengers of reactive oxygen species inhibits the development of complications and tissue damage in diabetic patients and experimental animals. 3,7 Ursodeoxycholic acid (UDCA) has been used for many years in the treatment of cholestatic liver diseases.…”