Alloxan toxicity in isolated rat hepatocytes and protection by sugars

Suspensions of isolated rat hepatocytes incubated in the presence of the diabetogenic agent alloxan exhibit time- and concentration-dependent damage. At concentrations of 3.5 mM and above, alloxan caused an increase in lactate dehydrogenase (LDH), glutamate-pyruvate transaminase (GPT) and intracellular potassium (K⁺) leakage, all of which are indices of plasma membrane damage, and decreased the intracellular reduced glutathione content (GSH) of the cells. Preincubation (10 min) in d-glucose (50 or 100 mM, but not 10 mM) partially protected the hepatocytes from LDH, GPT and K⁺ leakage and the decrease in GSH produced by alloxan (7mM) during a 60-min incubation period. Other sugars (d-galactose, 2-deoxy-d-glucose, d-fructose, d-mannoheptulose and d-mannitol) were also found to protect hepatocytes against damage caused by alloxan. d-Fructose was found to be the most potent protective sugar. These results indicate that alloxan is not selectively toxic to the pancreatic (β-cell and that sugars can protect against alloxan-induced cytotoxicity in hepatocytes.