Protective Effect of Glutathione and Cysteine Against Alloxan Diabetes in the Rat.

Abstract

The intraven. injn. of alloxan in doses of 40 mg./kg. produced diabetes in 95% of the animals. When glutathione or cysteine (neutralized to pH 7.4) was injected i.v. in doses of 2.0 mM/kg immediately preceding a diabeto-genic dose of alloxan, none of the animals developed diabetes. When the dose of the sulfhydryl compound was reduced to 1.0 mM/kg, partial protection occurred. Alanine 7.5 mM/kg, NaCl 7.5 mM/kg, phosphate buffer (pH 7.4) 2.5 mM/kg, and ascorbic acid 4.0-7.5 mM/kg did not exert any protective effect. Inasmuch as thioglycolic acid also protected against alloxan damage, it was concluded that the sulfhydryl group was responsible for the protective effect of cysteine and glutathione. Wheut cysteine in doses of 7.5 mM/kg was given 3-15 minutes following the injn. of alloxan, no protection occurred; whereas, when the cysteine was given within 1 min. following the alloxan, partial protection was observed. Although the mechanism of the sulfhydryl protection may simply consist in a reduction of alloxan to a non-diabetogenic compound, di-aluric acid, a more complex mechanism may be operating. It was suggested that the apparent selectivity of alloxan for the B-cells of the islets of the pancreas might be due to a low glutathione content.