Simferopol, Simferopol, Russian Federation
The necessity of modern research lies in the use of reliable experimental models of diabetes mellitus (DM) in animals, both for understanding the pathogenesis of the disease and for developing new pharmacological and non-pharmacological treatment methods. In experimental practice, the chemical model of DM, including the use of alloxan, is the most widespread. This model induces pronounced metabolic disorders in rats, accompanied by a persistent increase in blood glucose levels. Objective of the study: to identify the features of biochemical changes in the blood of rats with alloxan-induced DM in different experimental models. Alloxan-induced diabetes was induced in male Wistar rats (n=71) of average weight (272.32±22.70 g) and age (150.00±12.00 days) by intraperitoneal administration of alloxan monohydrate at doses of 150 mg/kg (2-All150; n=29), 200 mg/kg (3-All200; n=19), and 300 mg/kg (4-All300; n=13; fractionally, 3 times, 100 mg/kg every other day). Rats in group 1 (control, n=10) received an equivalent volume of physiological saline (0.2 ml). During the development of DM, body weight and peripheral blood glucose levels (from the tail tip) were measured dynamically on days 7, 14, 21, 28, and 31. After the experiment was concluded (day 32), key biochemical parameters were measured in blood serum, including glucose, total cholesterol, high- and low-density lipoproteins, triglycerides, total protein, urea, creatinine, and C-reactive protein. The measurements were performed using an automated biochemical analyzer ERBA-XL-180 («ErbaLachema», Czech Republic) with proprietary reagent kits designed for this device. The significance of differences between groups was assessed using Dunn’s nonparametric test. The results of the study showed that the mortality rate of experimental animals depended on the dose of alloxan and the administration method (single or fractional). In the second group (All150), mortality was 44.83 %; the highest was in the third group (All200) at 47.36 %; and the lowest was in the fourth group (All300) with fractional administration at 30.77 %. One month after alloxan administration, the animals developed DM, which was accompanied by polydipsia, polyuria, hyperglycemia, ketonuria, weight loss, dulling, darkening, and shedding of fur. The maximum increase in blood glucose concentration in group 4 rats was observed at the earliest stage (day 7; 20.3 mmol/L), while in group 3 rats, it peaked on day 14 (27.4 mmol/L). Changes in the biochemical parameters of rat serum in all experimental groups indicated significant disturbances in carbohydrate, lipid, and protein metabolism. However, the severity of these changes depended on the experimental model and the alloxan dose: fractional administration of alloxan at a dose of 300 mg/kg resulted in the most pronounced metabolic disturbances, while significantly reducing mortality.
diabetes mellitus; experimental models; alloxan-induced diabetes; biochemical blood parameters in rats; carbohydrate, lipid, and protein metabolism.
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