Abstract
Hepatitis poses a significant health issue worldwide as it may progress to cirrhosis and hepatocellular carcinoma. The crucial role of liver in different metabolic and synthetic functions of the body stimulates researchers to continually explore and develop different hepatoprotective drugs. The present study was designed to assess the potential hepatoprotective effect of deferasirox (DFX) in a rat model of acute liver injury induced by concanavalin A (Con A) at a dose of 20 mg/kg intravenously dissolved in normal saline solution. The hepatoprotective effect of DFX was screened at the doses (25, 50, and 100 mg/kg) via assessing the hepatotoxicity indices and histopathological examination. DFX at a dose of 100 mg/kg was the most effective in preventing the rise in activities of hepatotoxicity serum markers; alanine aminotransferase (ALT), and aspartate aminotransferase (AST) enzymes and histopathologic changes induced by con A.
Highlights
Liver diseases represent a critical public health problem globally because of the significant morbidity and mortality associated with it, which negatively affects the quality of life of the individuals.Concanavalin A (Con A)-induced liver injury is the most reliable animal model available nowadays for the study of viral and autoimmune hepatitis
Con A is a bean-derived lectin, that induces liver injury in mice mediated by the activated CD4+ T-cells (Tiegs et al, 1992)
Con A model of T-cell mediated liver injury can resemble auto-immune hepatitis, viral hepatitis, and the related acute liver failure (Tsutsui and Nishiguchi, 2014; Wang et al, 2012)
Summary
Concanavalin A (Con A)-induced liver injury is the most reliable animal model available nowadays for the study of viral and autoimmune hepatitis. Acute liver injury induced by con A depends on the activation of both adaptive and innate immune responses, CD4+ T-cells and natural killer cells (Tiegs et al, 1992), and it can resemble the immunologically-mediated liver damage in humans. Deferoxamine has been the iron chelator of choice since the 1970s (Neufeld, 2006), but the requirement for subcutaneous infusion of deferoxamine over 8 to 12 hours, 5 to 7 days a week and its associated side effects made it less compliant for patients (Cappellini, 2005; Modell et al, 2000; Olivieri and Brittenham, 1997). DFX showed anti-inflammatory, anti-oxidant, and hepatoprotective and cardioprotective effects in previous studies (Al-Rousan et al, 2011, 2009; Messa et al, 2010) which make it a promising candidate in our study
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