Chelating effects of siderophore in reducing organ dysfunction caused by iron overload in ICR mice

Thucydides L. Salunga, Isabella R. Panelo, Joel C. Cornista

Abstract


Background and Objectives: Iron is an essential element that plays a vital role in a wide variety of cellular processes but when present in excess concentration in organs it may increase the risk for liver disease, heart failure, and diabetes. Recently, siderophores which are iron-chelating agents produced by microorganisms have attracted tremendous attention because of its strong binding and high selectivity to the ferric form of iron. Thus, the use of siderophore in sequestering excess iron in the body as a form of therapy is very attractive. This study determined the effects of commercially available siderophore in sequestering excess iron in organs such as liver, heart, and pancreas under excess iron conditions.
Methodology: First, iron-overload was induced by injecting iron dextran (20 mg) into male ICR mice for three consecutive days. The effects of iron to the liver, heart, and pancreas and the possible sequestration by siderophore were determined by scoring histological sections. The liver iron concentration was also assessed by atomic absorption spectroscopy (AAS).
Results and Conclusion: The study showed that iron-overloaded mice exhibited skin hyperpigmentation and hemosiderosis in liver, heart, and pancreas. Significant changes in the liver include hepatomegaly and development of tumor. Iron-overloaded mice had 2,935% increase in liver iron content compared to the salinetreated mice. However, when iron-overloaded mice were treated with either 100 μg or 200 μg siderophore, there was a 77% and 84% decrease in liver iron content, respectively. Moreover, the treatment of ironoverloaded mice with siderophore prevented the development of hemosiderosis, tumor, and structural changes in the tissues studied. The results showed that siderophore can effectively reduce excess iron and organ damage in iron-overloaded mice and can be potentially employed in chelation therapy of iron-overload diseases. Further studies on the possible mechanisms of siderophore aside from decreasing iron excess and lowering organ dysfunction are recommended.


Keywords


siderophore; iron overload; iron chelating agents; hemosiderosis; hepatomagaly; hepatoprotection

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