Assessment of genotoxicity in rats treated with the antidiabetic drug Sitagliptin

This study aimed to find out the possible effects of stagliptin, the first representative of dipeptidyl peptidase (DPP-4) enzyme inhibitors, on body mass and blood glucose concentrations of rats. Similarly it is intended to measure the genetotoxic effects of stagliptin using single-cell gel test (Comet Assay).Forty male Wistar-Albino rats, 2 ? 3 months old, weighting 229.26 ± 28.92 g, were used in this study. Rats were fed by standart rat food and tap water was given ad libidum. Rats were allocateted into four groups each containing 10 rats. Group 1, control, was given only 1 ml of % 0.9 NaCl solution, Group 2: at 1 mg/kg dose, Group 3; at 10 mg/kg dose and Group 4: at 100 mg/kg dose active form of sitagliptin?s sitagliptin mono phosphate with 1 ml % 0.9 NaCl orally during 36 days were given. At the end of the study achieved values? mean standard deviations were determined and differences between groups were assesed on SPSS 11.5 packet programme in One-Way ANOVA variance analysis by Duncan test and t-test. The values under P<0.05 were assumed significant.In terms of he alive body mass values it was determined that pre application differences between groups kept going similar in 36th day, moreover the differences between 3th group and control group have vanished.The results of increasing alive body mass were between % 10 and % 20 and minimum % 10.05 in group 2 and % 10.62, % 13.62, % 18.59 by order of in control group, group 3 and group 4 were stated. In terms of blood glucose values there were no significant difference both between group control and group 4 and between all sitagliptin applying groups own were determined (P>0.05). It was stated that increasing blood glucose was between % 2.5 and % 14.25 and minimum in group 3 as % 2.5, % 9.37 and % 14.25 by order of in group 2 and group control (P >0.05), however it was in the level of % 7.53 (P<0.05) in group 4. In terms of the Genetic Damage Index (GDI) values were stated as 3.38 in H2O2?positive control group and as 0.72 minimum in control group and % 1.15, % 1.54, % 1.97 by order of group 3, group 4 and group 2.At the end of the application (36th day) by considering in all groups rats couldn?t reach to physiological alive body mass level and increasing were between % 10 and % 20 stated in physiological development period, increasing doses of sitagliptin did not cause any increasing or decreasing on alive body mass were determined. By comparing blood glucose levels with sitagliptin pre application it was stated that increasing ratio standed in physiological blood glucose interval, especially alive body mass in rats and when it has been compared with control group, active and high doses of sitagliptin did not cause importantly increasing or decreasing on blood glucose level, thus its hypoglicaemic risk was rather low. It was determined that damaged cell ratio and GDI values in in vitro rat leucocytes didn?t change in the same way, consequently DNA damage did not relate directly to drug application; in diabetes developed animals, during different periods and in different doses including sitagliptin use more comprehensive studies?s necessarity was determined.Key words: Comet assay, DNA damage, DPP-4 enzyme inhibitor, genotoxicity, rat, sitagliptin.