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 (7 mM) 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 beta-cell and that sugars can protect against alloxan-induced cytotoxicity in hepatocytes.
D000496:Alloxan / Q000633:toxicity*; D000818:Animals; D002241:Carbohydrates / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000517:prevention & control*; D005947:Glucose / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002241:Carbohydrates; D000496:Alloxan; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D005947:Glucose