Anti-Oxidant and Anti-Inflammatory Effects of Vildagliptin in NonAlcoholic Fatty Liver Disease of Mice

Abstract

Background: Vildagliptin is one of the Dipeptidyl Peptidase-4 (DPP-4) inhibitors. It is used as a novel oral anti-diabetic drug for the treatment of Type 2 Diabetes Mellitus (T2DM) with significant control of glycated hemoglobin and a lower incidence of hypoglycemia or weight gain. Aim: The present study hypothesized that the DPP-4 inhibitor vildagliptin may exert protective effects on liver in Non-Alcoholic Fatty Liver Disease (NAFLD) in cholesterol-fed albino mice. Methods: Thirty six albino mice were divided into 3 group (n=12). Group 1 (control) received distilled water and fed normal diet. Group 2 fed high cholesterol diet without therapy. The third group was fed with cholesterol rich diet and daily treated with vildagliptin (15 mg/ kg/day for 12 weeks). Liver index, liver triglyceride contents, serum hepatic transaminases, some anti-oxidant enzymes and TNF-α levels were measured in all groups. Results: Administration of vildagliptin in cholesterol-fed mice attenuated the development of NAFLD via a significant (p<0.05) decrease in ALT & AST liver enzymes versus NAFLD non-treated group (33.43 ± 6.0 & 34.13 ± 4.7U/L versus 344.9 ± 12.1 & 278.9 ± 5.9 respectively). Additionally, both liver triglyceride contents and tumor necrosis factor-alpha (TNF-α) were significantly (p<0.05) reduced in treated group 3 compared to cholesterol-fed non-treated groups (for liver triglycerides: 12.61 ± 0.41 versus 56.41 ± 2.11 mg/g tissue protein respectively while for TNF-α: 1.25 ± 0.75 versus 10.78 ± 1.18pg/mL respectively). Meanwhile, it produced a significant (p<0.05) increase in the levels of measured serum antioxidant markers in group 3 versus group 2 as follow: (SOD enzyme: 37.5 ± 4.24 versus 0.84 ± 0.43IU/mL, TBARS: 3.46 ± 0.66 versus 62.5 ± 3.3nmol/mg hepatic tissue protein, Catalase enzyme 54.7 ± 3.45 versus 4.51 ± 0.32 and GPx enzyme 17.34 ± 0.79 versus 0.21 ± 0.02 unit/mg hepatic tissue protein, respectively). Conclusion: These results suggest possible anti-oxidant and partial anti-inflammatory mechanisms in therapy of NAFLD by this anti-diabetic drug.