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- W4313359122 abstract "Abstract Background Iron is highly reactive and could induce oxidative stress via augmenting the activity of heme enzymes, i.e., NADPH oxidase and myeloperoxidase (MPO). Unlike the membrane-restricted NADPH oxidase, MPO remains active upon its release into circulation and thus may potentially exacerbate iron-induced oxidative damage. Objective To investigate the extent to which MPO is involved in iron-induced toxicity. Methods Acute toxicity was induced by intraperitoneal injection of FeSO4 to MPO deficient (MPOKO) mice and their WT littermates. In some studies, WT mice were pretreated with 4-aminobenzoic acid hydrazide (a MPO inhibitor). Chronic toxicity was induced by feeding 2% carbonyl iron-diet to WT and MPOKO mice. Iron status, MPO levels, inflammatory (SAA, lipocalin 2, KC, IL-6 and IL-1β), organ damage (AST, ALT) and oxidative stress (MDA) markers were assessed. Results Acute iron administration upregulated circulating MPO in WT mice, which may be due to increased neutrophil degranulation or oxidative burst. However, the loss of MPO activity in mice, either via inhibition or genetic deficiency, markedly reduced iron-induced organ damage and systemic inflammation. In contrast, long-term iron feeding to WT mice reduced circulating MPO, but promoted its accumulation in liver. While both MPOKO and WT mice showed similar levels of diet-induced hyperferremia, MPOKO mice displayed significantly reduced inflammatory response and oxidative stress. Conclusion Genetic deficiency or pharmacologic inhibition of MPO substantially attenuated acute and chronic iron-induced toxicity. Our results suggest that targeting MPO during iron overload may be a promising approach to reduce iron-induced toxicity/side effects." @default.
- W4313359122 created "2023-01-06" @default.
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- W4313359122 date "2018-05-01" @default.
- W4313359122 modified "2023-09-24" @default.
- W4313359122 title "Myeloperoxidase Deficiency Attenuates Dietary and Systemic Iron-induced Toxicity" @default.
- W4313359122 doi "https://doi.org/10.4049/jimmunol.200.supp.170.8" @default.
- W4313359122 hasPublicationYear "2018" @default.
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