Iron chelation by deferasirox confers protection against concanavalin A-induced liver fibrosis: A mechanistic approach.

Iron chelation by deferasirox confers protection against concanavalin A-induced liver fibrosis: A mechanistic approach. Toxicol Appl Pharmacol. 2019 Sep 06;:114748 Authors: Adel N, Mantawy EM, El-Sherbiny DA, El-Demerdash E Abstract Hepatic iron overload is one of the causative factors for chronic liver injury and fibrosis. The present study aimed to investigate the potential antifibrotic effect of the iron chelator; deferasirox (DFX) in experimentally-induced liver fibrosis in rats. Male Sprague-Dawley rats were administered concanavalin A (Con A) and/or DFX for 6 consecutive weeks. Con A injection induced significant hepatotoxicity as was evident by the elevated transaminases activity, and decreased albumin level. Also, it disturbed the iron homeostasis through increasing C/EBP homologous protein (CHOP), decreasing phosphorylated cAMP responsive element binding protein(P-CREB) and hepcidin levels leading to significant serum and hepatic iron overload. In addition, it induced an imbalance in the oxidative status of the liver via upregulating NADPH oxidase 4 (NOX4), together with a marked decrease in anti-oxidant enzymes' activities. As a consequence, upregulation of nuclear factor-kappa b (NF-κB) and the downstream inflammatory mediators was observed. Those events all together precipitated in initiation of liver fibrosis as confirmed by the elevation of alpha-smooth muscle actin (α-SMA) and liver collagen content. Co-treatment wit...
Source: Toxicology and Applied Pharmacology - Category: Toxicology Authors: Tags: Toxicol Appl Pharmacol Source Type: research