ACTA ENDOCRINOLOGICA (BUC)

Background. Linagliptin (LNG) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that ameliorates blood glucose control of patients with type 2 diabetes, without developing hypoglycemic risk and weight gain with a good clinical and biological tolerance profile. To the best of our knowledge, its cytotoxic, genotoxic and oxidative effects have never been studied on any cell line. Aim. To evaluate the in vitro cytotoxic, genotoxic damage potential and antioxidant/oxidant activity of LNG in cultured peripheral blood mononuclear cells (PBMC). Material and methods. After exposure to different doses (from 0.5 to 500 mg/L) of LNG, cell viability was measured by the MTT (3,(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) and lactate dehydrogenase (LDH) leakage tests. The antioxidant activity was assessed by the total antioxidant capacity (TAC) and total oxidative stress (TOS) assays. To evaluate the genotoxic damage potential, chromosomal aberration (CA) frequencies and 8-oxo-2’- deoxyguanosine (8-oxo-dG) levels were determined. Results. Treatment with LNG did not cause statistically significant decreases of cell viability at lower concentrations than 100 mg/L as compared to untreated cultures. However, LNG exhibited cytotoxic action at 250 and 500 mg/L. Also, IC20 and IC50 values of LNG were determined as 8.827 and 70.307 mg/L, respectively. In addition, the oxidative analysis revealed that LNG supported antioxidant capacity at concentrations of 2.5, 5, 10, 25, 50 and 100 mg/L without generating oxidative stress. Besides, the results of CA and 8-oxo-dG assays showed in vitro nongenotoxic feature of LNG. As a conclusion, our findings clearly revealed that LNG had no cytotoxic and genotoxic actions, but exhibited antioxidative activity. In conclusion, therefore it is suggested that LNG use in diabetic patients is safe and provides protection against diabetic vascular and oxidative complications.

Aim. The aim of this study was to investigate the dose-dependent effects of prednisolone administration on serum vaspin levels and correlate this with changes in the BMI and lipogenesis in rats. Materials and Methods. Twenty-four albino Wistar male rats weighing between 190–240 g were divided into four groups, three experimental (5 mg/kg, 10 mg/kg, and 20 mg/kg prednisolone) and one control. The prednisolone groups were given once-daily doses for 30 days, orally. In addition, the rats were weighed, and their height and waist circumferences were measured once a week. At the end of 30 days, vaspin and glucose levels were measured from blood samples. Results. In the prednisolone groups, the vaspin levels significantly increased when compared with the control group. The control group has a serum vaspin level of 155 ± 20.99 pg/mL and this level has been increased by prednisolone administration in a dose dependent manner. In the prednisolone groups, especially the 10 mg/kg and 20 mg/ kg groups, the glucose levels increased in a dose dependent fashion. Conclusion. Prednisolone administration significantly increased serum glucose and vaspin levels in a dose dependent manner, indicating that the increase in the serum vaspin levels could be related to the increase in the serum glucose concentration. Vaspin can be a molecule that is released in response to increased glucose and can be a rebound defense mechanism to modulate the blood glucose concentration. We suggest vaspin as a potential target for the treatment and diagnosis of diabetes mellitus and other metabolic disorders.