Comparative study of different models of alloxan-induced diabetes mellitus

Abstract

Aim. To compare the clinical course of diabetes mellitus induced by alloxan using classic and modified technique. Methods. Experiments were carried out on mature white mongrel rats, which were divided into two groups: the first group (25 rats) was administered a 200 mg/kg single dose of alloxan (classic model), the second group (25 rats) was administered 150 mg/kg of alloxan at the first day, 100 mg/kg of alloxan at the second day and 100 mg/kg of alloxan at the fourth day. 25 intact rats were examined as a control group. The animals were withdrawn from the experiment by decapitation on the 10th and 21st day, blood and tissue samples were taken for the laboratory testing. The animals’ status (mortality, grooming behavior, body weight, food and water intake) were measured by visual examination. The levels of glucose and lipids were assessed using enzyme colorimetric detection («Human» laboratory kits, Germany, FP-901 analyzer), insulin and C-peptide levels were examined by enzyme-linked immunosorbent assay («Chemwell» analyzer, «DEMENITECKILL-WELLSEE» laboratory kits, Germany); levels of diene conjugates and malonic dialdehyde - using the photocolorimetry based on the colored thiobarbituric acid products. Results. In the first group, the mortality reached 68%, mean weight loss - 41.2%. Blood glucose level at the 10th and 21st days was higher by 370.7 и 146.2% respectively compared to intact animals. Insulin level decreased by 95.8 and 83.7%, C-peptide level - by 96 and 83.7%. In the second group, mortality was 32%, mean body weight loss - 36.5%, blood glucose level at the 10th and 21st days elevated by 364.5 and 151.5%, insulin level decreased by 96.1 and 82.9%, C-peptide level - by 96.0 and 83.7% respectively. A moderate hyperlipidemia was observed in both groups with increased levels of cholesterol, triglycerides, low and very-low density lipoproteids, free fatty acids and decreased levels of high density lipoproteids. The concentration of diene conjugates and malonic dialdehyde increased rapidly to a variable degree depending on the tissue anti-oxidative activity. Conclusion. When diabetes mellitus is modeled by the use of alloxan, an acute form of alloxan-induced diabetes is observed on the 10th day, a chronic form - on the 21st day in both groups. The modified model of alloxan-induced diabetes showed 36% less mortality rate compared to the classic model.