Vildagliptin, a DPP-4 inhibitor, attenuates carbon tetrachloride-induced liver fibrosis by targeting ERK1/2, p38 α, and NF-κB signaling.

Vildagliptin, a DPP-4 inhibitor, attenuates carbon tetrachloride-induced liver fibrosis by targeting ERK1/2, p38α, and NF-κB signaling. Toxicol Appl Pharmacol. 2020 Sep 18;:115246 Authors: Khalil R, Shata A, Abd El-Kader EM, Sharaf H, Abdo WS, Amin NA, Saber S Abstract Mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-ĸB signaling have been recognized for their causal connection with liver fibrosis. Hence, it is encouraging to discover drugs that can modify the interactions between these signaling cascades. It has been suggested that glucagon-like peptide-1 receptors (GLP-1Rs) might have a role in the observed hepatoprotection of dipeptidyl peptidase-4 inhibitors other than vildagliptin (VLD). Consequently, we aimed to elucidate the mechanisms underlying its potential antifibrotic activity in a CCl4-intoxicated mouse model. VLD increased the percentage of viable CCl4-intoxicated primary rat hepatocytes in vitro. It also attenuated hepatic fibrosis, improved liver function, and prolonged survival of CCl4-intoxicated mice in a dose-dependent manner. This hepatoprotection might be mediated mainly through interference with extracellular signal-regulated protein kinase 1/2 phosphorylation, the most downstream signal of the MAPK pathway. In addition, VLD hepatoprotective activity could be partially mediated through inhibition of p38α phosphorylation and phosphorylation-induced NF-ĸB activation. As a result, VLD downreg...
Source: Toxicology and Applied Pharmacology - Category: Toxicology Authors: Tags: Toxicol Appl Pharmacol Source Type: research