Myeloperoxidase deficiency attenuates systemic and dietary iron-induced adverse effects

The Journal of Nutritional Biochemistry
Xia XiaoMatam Vijay-Kumar

Abstract

Iron deficiency is routinely treated with oral or systemic iron supplements, which are highly reactive and could induce oxidative stress via augmenting the activity of proinflammatory enzyme myeloperoxidase (MPO). To investigate the extent to which MPO is involved in iron-induced toxicity, acute (24 h) iron toxicity was induced by intraperitoneal administration of FeSO4 (25 mg/kg body weight) to MPO-deficient (MpoKO) mice and their wild-type (WT) littermates. Acute iron toxicity was also assessed in WT mice pretreated with an MPO inhibitor, 4-aminobenzoic acid hydrazide. Systemic iron administration up-regulated circulating MPO and neutrophil elastase and elevated systemic inflammatory and organ damage markers in WT mice. However, genetic deletion of MPO or its inhibition significantly reduced iron-induced organ damage and systemic inflammatory responses. In contrast to the acute model, 8 weeks of 2% carbonyl iron diet feeding to WT mice did not change the levels of circulating MPO and neutrophil elastase but promoted their accumulation in the liver. Even though both MpoKO and WT mice displayed similar levels of diet-induced hyperferremia, MpoKO mice showed significantly reduced inflammatory response and oxidative stress than t...Continue Reading

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Citations

Sep 17, 2019·Alcoholism, Clinical and Experimental Research·Nipun SainiSusan M Smith
Sep 10, 2019·Frontiers in Immunology·Bernardo FariaMarc A Seelen
Sep 19, 2020·International Journal of Molecular Sciences·Jean-Baptiste Michel, José Luis Martin-Ventura

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