Sitagliptin ameliorates thioacetamide-induced acute liver injury via modulating TLR4/NF-KB signaling pathway in mice

Abstract

Sitagliptin is an oral hypoglycemic drug that acts by selective inhibition of dipeptidyl peptidase-4 (DDP-4) enzyme.

Aim: This study scrutinized the hepatoprotective impact of sitagliptin) against thioacetamide (TAA)-induced liver damage in mice.

Main methods: Male mice were injected with TAA (500 mg/kg) then treated with sitagliptin (20 mg/kg) orally for 5 days.

Key findings: Histopathological results of TAA group revealed severe degree of centrolobular hepatic necrosis. Additionally, biochemical findings showed marked elevation in the serum transaminases and gamma glutamyl transpeptidase (GGT) levels in TAA group. Injection of TAA significantly disrupted oxidant/antioxidants hemostasis of the hepatic tissues. Also, TAA markedly increased the expression of nuclear factor kappa-B (NF-KB); and enhanced Toll like receptor 4 (TLR4) as well as NLPR3 inflammosome production. Moreover, there was an elevation in the hepatic levels of tumor necrosis factor-alpha (TNF-α) and interleukin -1 beta (IL-1β) besides increased immunoexpression of Bcl-2-associated X protein (Bax) as well as caspase 3. In contrast, treatment with sitagliptin significantly attenuated TAA-induced histopathological, biochemical and immunohistochemical alterations.

Significance: Our results suggest that the hepatoprophylactic impact of sitagliptin might be arbitrated via modulating TLR4 and NK-KB signaling cascade followed by depression of inflammation besides apoptosis.

Keywords: Bax; Caspase3; NF-KB; NLRP3; Sitagliptin; TLR4.