Hepatoprotective role of vildagliptin in CLP-induced sepsis in mice

Aim: The current study aimed to determine the underlying mechanisms of protective effect of vildagliptin against sepsis induced liver injury.

Materials and methods: Male mice were randomly allocated to sham group, Cecal Ligation and Puncture group, Dimethyl sulfoxide group and vildagliptin group (20 mg/kg). Cecal Ligation and Puncture operation was established for mice. After 24 hours of Cecal Ligation and Puncture, serum levels of Alanine Transaminase, Aspartate Transaminase and histopathological changes of liver tissue were evaluated. Our study assessed IL-6, Macrophage migration inhibitory factor, Intercellular Adhesion Molecule 1, caspase-11, Malondialdehyde, Superoxide dismutase and Microtubule-associated protein 1A/1B-light chain 3 by ELISA method as well as Wnt and B-catenin by RT‑qPCR.

Results: The results of current study showed that vildagliptin administration significantly declined serum levels of Alanine Transaminase and Aspartate Transaminase in addition to reduced histopathological changes of liver. Vildagliptin markedly inhibited elevation of IL-6, MIF, Intercellular Adhesion Molecule 1, MDA, caspase-11 and Wnt/B-catenin. Vildagliptin elevated Superoxide dismutase and Microtubule-associated protein 1A/1B-light chain 3 in hepatic tissue.

Conclusions: Vildagliptin has Hepatoprotective effect during endotoxemia induced liver injury through modulation inflammatory and oxidative stress markers in addition to down regulation of Wnt/B-catenin pathway.