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IRP1 Activity and Expression Are Increased in the Liver and the Spleen of Rats Fed Fish Oil–Rich Diets and Are Related to Oxidative Stress

Silvia Miret^*,, Andrew T. McKie, María P. Sáiz^*, Adrian Bomford^** and María T. Mitjavila^*,3

^* Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain, Division of Life Sciences and ^** Institute of Liver Studies, King’s College Hospital, London, UK

³To whom correspondence should be addressed. E-mail: mmitjavila{at}ub.edu.

Many clinical studies have indicated that diets rich in fish oil (FO) reduce the risk of cardiovascular disease and have anti-inflammatory and antithrombotic properties. Although the therapeutic effects of FO have been well described, their impact on iron metabolism remains unclear. The aim of this work was to study the activity and expression of IRP1 in the liver and the spleen of rats fed FO-rich diets with 0 (FO-0) or 100 (FO-1) mg/kg of all-rac--tocopherol acetate. We also measured nonheme iron, -tocopherol and retinol concentrations, and superoxide (SOD) and catalase activity in these organs. Rats fed FO were compared to rats fed a corn oil (CO)–rich diet with 100 mg/kg all-rac--tocopherol acetate. The activity and expression of IRP1 in both the liver and the spleen of rats fed FO diets were greater than in those fed the CO diet. FO-fed rats also had lower nonheme iron concentrations in these organs. Hepatic -tocopherol and retinol concentrations and SOD activity were lower in FO-0–fed rats compared to those fed the CO diet. In the spleen, -tocopherol and retinal concentrations were not altered but SOD activity was lower in FO-0– fed rats, whereas catalase activity was greater than in rats fed CO. The results indicate that there is an increase in oxidative stress in the liver and in the spleen of rats fed FO diets. These changes, together with the reduction of nonheme iron concentrations in both FO-0– and FO-1–fed rats, may explain the increase in activity and expression of IRP1. Therefore, the ingestion of FO-rich diets should be monitored under close supervision.

KEY WORDS: • antioxidants • corn oil • fish oil • iron • IRP1 • rats