In thalassemia, iron overload is the joint outcome of excessive iron absorption and transfusional siderosis. While iron absorption is limited by a physiologic ceiling of about 3 mg/d, plasma iron turnover in thalassemia may be 10 to 15 times normal, caused by the wasteful, ineffective erythropoiesis of an enormously expanded erythroid marrow. This outpouring of catabolic iron exceeds the iron-binding capacity of transferrin and appears in plasma as non-transferrin-plasma iron (NTPI). The toxicity of NTPI is much higher than of transferrin-iron as judged by its ability to promote hydroxyl radical formation resulting in peroxidative damage to membrane lipids and proteins. In the heart, this results in impaired function of the mitochrondrial respiratory chain and abnormal energy metabolism manifested clinically in fatal hemosiderotic cardiomyopathy. Ascorbate increases the efficacy of iron chelators by expanding the intracellular chelatable iron pool, but, at suboptimal concentrations is a pro-oxidant, enhancing the catalytic effect of iron in free radical formation. NTPI is removed by i.v. DFO in a biphasic manner and reappears rapidly upon cessation of DFO, lending support to the continuous, rather than intermittent, use of chelators. Unlike DFO and other hexadentate chelators, bidentate chelators such as L1 may produce incomplete intermediate iron complexes at suboptimal drug concentrations.

Abstract-The most known risk factor for nonalcoholic fatty liver disease (NAFLD) is the metabolic syndrome. In this study, we characterized changes in liver pathology, hepatic lipid composition, and hepatic iron concentration (HIC) occurring in rats given fructose-enriched diet (FED), with and without therapeutic maneuvers to reduce blood pressure and plasma triglycerides. Rats were given FED or standard rat chow for 5 weeks. Rats on FED were divided into 4 groups: receiving amlodipine (15 mg/kg per day), captopril (90 mg/kg per day), bezafibrate (10 mg/kg per day) in the last 2 weeks, or a control group that received FED only. FED rats had hepatic macrovesicular and microvesicular fat deposits develop, with increase in hepatic triglycerides (ϩ198%) and hepatic cholesterol (ϩ89%), but a decrease in hepatic phospholipids (Ϫ36%), hypertriglyceridemia (ϩ223%), and hypertension (ϩ15%), without increase in HIC. Amlodipine reduced blood pressure (Ϫ18%), plasma triglycerides (Ϫ12%), but there was no change in hepatic triglycerides and phospholipids concentrations. Captopril reduced blood pressure (Ϫ24%), plasma triglycerides (Ϫ36%), hepatic triglycerides (Ϫ51%), and hepatic macrovesicular fat (Ϫ51%), but increased HIC (ϩ23%), with a borderline increase in hepatic fibrosis. Bezafibrate reduced plasma triglycerides (Ϫ49%), hepatic triglycerides (Ϫ78%), hepatic macrovesicular fat (Ϫ90%), and blood pressure (Ϫ11%