1. Chronic Deferasirox Administration Decreases Hepatic Oxidative Stress and Apoptosis in the Iron Overloaded Gerbil
- Author
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Ernest M. Walker, Satyanarayana Paturi, Brent Kidd, Anjaiah Katta, Eric R. Blough, Kamran Manzoor, and Rabaa M. Al-Rousan
- Subjects
medicine.medical_specialty ,Cirrhosis ,biology ,business.industry ,Immunology ,Deferasirox ,Cell Biology ,Hematology ,Hemosiderosis ,medicine.disease ,medicine.disease_cause ,Biochemistry ,Ferritin ,Endocrinology ,Internal medicine ,medicine ,biology.protein ,Iron Dextran Complex ,Hepatic fibrosis ,business ,Hemochromatosis ,Oxidative stress ,medicine.drug - Abstract
Abstract 1996 Poster Board I-1018 Background: Iron overload occurs under conditions such as primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis) and is associated with an increased risk of developing liver fibrosis, cirrhosis, and hepatocellular carcinoma. Deferasirox is a novel oral chelator with high iron-binding potency and selectivity. Here we investigate the ability of deferasirox to remove excessive hepatic iron and prevent or reverse iron induced hepatic injury. Methods: Adult male Mongolian Gerbils were randomly divided into three groups: control, iron overload, and iron overload + deferasirox treatment (n = 8 / group). Iron overload animals received iron dextran 100mg/kg i.p /5d for 10 wks while deferasirox was given 100mg/kg/d p.o for 1-,3-, or 9- months. Hepatic iron levels were determined by inductively coupled plasma atomic emission spectrometry and Prussian blue staining was performed to examine iron deposition in the corresponding tissues. Immunoblot and immunohistochemical analyses for markers of oxidative stress were employed to assess effects of deferasirox treatment on hepatic protein oxidation and superoxide levels. TUNEL assay was employed to examine the extent of hepatic apoptosis. Results: Compared to the non-treated iron overload group, deferasirox treatment reduced hepatic iron levels by 21.3%, 43.5%, and 47.4% after 1, 3, and 9 months of treatment, respectively (p Conclusions: These findings suggest that chronic deferasirox treatment may decrease iron-induced hepatic oxidative stress and apoptosis. Decrease in ROS accumulation in the liver may be the possible mechanism of this protective effect. Further studies are underway to delineate specific mechanisms. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2009