High sensitivity to streptozotocin in herbivorous voles, Microtus arvalis, compared to mice

Herbivorous voles, Microtus arvalis, have characteristics similar to herbivores in that their hepatic glycolytic enzyme activities are relatively low. The effects of a single low dose (100 mg/kg body weight) of streptozotocin (STZ) in voles were studied and the difference in sensitivity to or toxicity of STZ in voles and C57BL/6 mice was compared. In voles which received STZ, the cumulative incidence of glycosuria reached 53% by 4 weeks after administration. The diabetic voles showed marked increases in their blood glucose and plasma free fatty acid concentrations and a significant decrease in plasma immunoreactive insulin concentrations. Their hepatic hexokinase, glucokinase, glutathione peroxidase and glutamate dehydrogenase activities decreased significantly and lesions were widely observed in the liver, kidney and pancreas. The activities of glutathione peroxidase, a scavenger of H2O2, decreased significantly in their liver and pancreas. These changes were not observed in C57BL/6 mice which received STZ. The higher sensitivity to and toxicity of STZ in voles than in mice are considered to be caused by the characteristically low activities of glycolytic enzymes and glutathione peroxidase in the tissues of voles. Voles may be a good model for studying the mechanisms of cytotoxicity by STZ in herbivorous animals.