Myeloperoxidase deficiency attenuates systemic and dietary iron-induced adverse effects

Xia Xiao, Piu Saha, Beng San Yeoh, Jennifer A. Hipp, Vishal Singh, Matam Vijay-Kumar

Research output: Contribution to journalArticle

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 the WT mice. In addition, WT bone-marrow-derived neutrophils (BMDN) generated more reactive oxygen species than MPO-deficient BMDN upon iron stimulation. Altogether, genetic deficiency or pharmacologic inhibition of MPO substantially attenuated acute and chronic iron-induced toxicity. Our results suggest that targeting MPO during iron supplementation is a promising approach to reduce iron-induced toxicity/side effects in vulnerable population.

Original languageEnglish (US)
Pages (from-to)28-34
Number of pages7
JournalJournal of Nutritional Biochemistry
Volume62
DOIs
StatePublished - Dec 1 2018

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Dietary Iron
Peroxidase
Iron
Toxicity
Leukocyte Elastase
Oxidative stress
Nutrition
Myeloperoxidase Deficiency
Bone
Oxidative Stress
Neutrophils
Bone Marrow
Diet
Vulnerable Populations
Liver
Reactive Oxygen Species

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Xiao, Xia ; Saha, Piu ; Yeoh, Beng San ; Hipp, Jennifer A. ; Singh, Vishal ; Vijay-Kumar, Matam. / Myeloperoxidase deficiency attenuates systemic and dietary iron-induced adverse effects. In: Journal of Nutritional Biochemistry. 2018 ; Vol. 62. pp. 28-34.
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Myeloperoxidase deficiency attenuates systemic and dietary iron-induced adverse effects. / Xiao, Xia; Saha, Piu; Yeoh, Beng San; Hipp, Jennifer A.; Singh, Vishal; Vijay-Kumar, Matam.

In: Journal of Nutritional Biochemistry, Vol. 62, 01.12.2018, p. 28-34.

Research output: Contribution to journalArticle

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AU - Xiao, Xia

AU - Saha, Piu

AU - Yeoh, Beng San

AU - Hipp, Jennifer A.

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AU - Vijay-Kumar, Matam

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