Induction of hyperglycemia and accompanying biochemical and genotoxic changes in mice of different strains by tyloxapol

Abstract

Introduction. Hyperglycemia inducers, the «classic» diabetogens streptozotocin and alloxan have a pronounced effect and are therefore limited suitable for modeling mild hyperglycemia in an experiment. Tyloxapol (Triton WR1339) was chosen as an alternative agent for modeling a moderate increase in blood glucose concentration in experimental animals based on literature data. The purpose of the study. The aim of the work was to investigate the possibility of tyloxapol to induce hyperglycemia and concomitant biochemical and genotoxic changes in mice of the common C57BL/6, CBA/lac and ICR lines. Methods. Hyperglycemia was modeled by single or multiple administration of tiloxapol at a dose of 400 mg/kg intraperitoneally. 24 hours after the last injection of tyloxapol, glucose and lipid levels were determined in mouse blood samples, DNA damage was assessed in organs by the DNA comet method, and chromosomal aberrations were recorded in bone marrow cells. Results. It was found that tyloxapol at a dose of 400 mg/kg with different modes of administration to mice of different lines similarly causes moderate hyperglycemia and a significant increase in triglycerides, total cholesterol and low-density lipoproteins, as well as an increase in DNA damage, which is considered as a trigger for many complications in diabetes. Conclusion. The data obtained in mice are consistent with the literature data on the hyperglycemic activity of tyloxapol, previously established in rats, and demonstrate characteristic biochemical and genotoxic effects in mice of different lines, with less severity in animals of the ICR line. In general, the data obtained indicate the possibility of using tiloxapol to model experimental diabetes in mice.