Effects of Sitagliptin on oxidative stress metabolism in liver and kidney tissues in rats

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 and also to assess the possible damage of oxidative stress in liver and kidney tissues, measuring by the level of superoksit dismutaz (SOD, U/mg tissue protein) and catalaz (CAT, k/mg tissue protein) enzyme activity, glutatyon (GSH, mg/mg tissue protein) level and malondialdehid (MDA, nmol/mg tissue protein) concentrations in rats following administration with increased doses.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.Comparing the liver and left kidney tissue weights; there was a significant difference between groups 3 and 4, and also between group 2 and the other groups. In terms of the right kidney tissue weights, group 3 and the control group with other groups, and similarly revealed significant difference between group 2 and group 3.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, however it was in the level of % 7.53 in group 4.It was determined that the increase in body weight (10-20 %) to fall within the physiological development, tissue weight gains were increased in parallel with the body weight and organ development. Moreover, it was found that the elevations of blood glucose levels (2,5-14,25 %) were in physiological range. Accordingly, it was observed that the selected doses of sitagliptin didn?t cause significant changes in body and tissue weights, and the risk of hypoglycemia was lower.Although the increasing of MDA concentration and the antioxidant enzyme activities in the liver, do not cause lipid peroxidation (MDA level) in liver and kidney tissue; following daily 10 and 100 mg / kg dose of sitagliptin administration, GSH level increased significantly compared with the control group in liver tissue. Moreover, in term of CAT enzyme activity in renal tissue, it was determined that all three doses of sitagliptin administrations caused significant decrease compare to the control group.It was concluded that data only obtained from heart and kidney tissues may not be enough to determine completely the effects of sitagliptin?s oxidant - antioxidant balance; in animals in which different experimental models are generated into a wider parameters, involving the use of sitagliptin?s different dosages and durations of making comprehensive studies may help to clarify the effect of the drug on the mechanism of oxidative stress.