The A3 adenosine receptor agonist, namodenoson, ameliorates non ‑alcoholic steatohepatitis in mice.

The A3 adenosine receptor agonist, namodenoson, ameliorates non‑alcoholic steatohepatitis in mice. Int J Mol Med. 2019 Oct 03;: Authors: Fishman P, Cohen S, Itzhak I, Amer J, Salhab A, Barer F, Safadi R Abstract The Wnt/β‑catenin pathway confers a chain of molecular events in livers affected by non‑alcoholic steatohepatitis (NASH). Namodenoson, a selective agonist of the A3 adenosine receptor (A3AR), which is highly expressed in pathological liver cells, induces a robust anti‑inflammatory effect in the liver, mediated via the de‑regulation of the Wnt/β‑catenin pathway. Namodenoson also acts as a liver protective agent by inhibiting ischemia/reperfusion injury. Based on these unique characteristics, we investigated the anti‑NASH effect of Namodenoson in murine models of steatohepatitis and in the LX2 human hepatic stellate cell line (HSC). In the STAM model, Namodenoson significantly decreased the non‑alcoholic fatty liver disease (NAFLD) activity score, NAS, demonstrating anti‑inflammatory and anti‑steatotic effects. In the carbon tetrachloride (CCl4) model, Namodenoson reversed alanine aminotransferase (ALT) to normal values and significantly improved liver inflammation and fibrosis, as well as the adiponectin and leptin levels. Namodenoson de‑regulated the Wnt/β‑catenin pathway in the liver extracts of the CCl4 model mice and in the LX2 HSCs, manifested by a decrease in the expression of phosphoino...
Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Tags: Int J Mol Med Source Type: research