Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 382, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2019.114748
Keywords
Liver fibrosis; Iron overload; Concanavalin A; Deferasirox; Hepcidin
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Funding
- Egyptian Ministry of Scientific Research [12-2-4]
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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-kappa B) 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 (alpha-SMA) and liver collagen content. Cotreatment with DFX protected against experimentally-induced liver fibrosis in rats via its iron chelating, antioxidant, and anti-inflammatory properties. These findings imply that DFX can attenuate the progression of liver fibrosis.
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