ArticlePloS one2015
Melatonin prevents myeloperoxidase heme destruction and the generation of free iron mediated by self-generated hypochlorous acid.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 19 citations in OpenAlex.
- Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor.Orphanet journal of rare diseases · 2023Article
- Grape Pomace as a Cardiometabolic Health-Promoting Ingredient: Activity in the Intestinal Environment.Antioxidants (Basel, Switzerland) · 2023Review
- Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer.Frontiers in oncology · 2022Review
- Deficient synthesis of melatonin in COVID-19 can impair the resistance of coronavirus patients to mucormycosis.Medical hypotheses · 2021Article
- Melatonin interferes with COVID-19 at several distinct ROS-related steps.Journal of inorganic biochemistry · 2021Review
- Melatonin prevents hypochlorous acid-mediated cyanocobalamin destruction and cyanogen chloride generation.Journal of pineal research · 2018Article
- Oral Mucositis: Melatonin Gel an Effective New Treatment.International journal of molecular sciences · 2017Review
- The Impact of Myeloperoxidase and Activated Macrophages on Metaphase II Mouse Oocyte Quality.PloS one · 2016Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
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Abstract
Myeloperoxidase (MPO) generated hypochlorous acid (HOCl) formed during catalysis is able to destroy the MPO heme moiety through a feedback mechanism, resulting in the accumulation of free iron. Here we show that the presence of melatonin (MLT) can prevent HOCl-mediated MPO heme destruction using a combination of UV-visible photometry, hydrogen peroxide (H2O2)-specific electrode, and ferrozine assay techniques. High performance liquid chromatography (HPLC) analysis showed that MPO heme protection was at the expense of MLT oxidation. The full protection of the MPO heme requires the presence of a 1:2 MLT to H2O2 ratio. Melatonin prevents HOCl-mediated MPO heme destruction through multiple pathways. These include competition with chloride, the natural co-substrate; switching the MPO activity from a two electron oxidation to a one electron pathway causing the buildup of the inactive Compound II, and its subsequent decay to MPO-Fe(III) instead of generating HOCl; binding to MPO above the heme iron, thereby preventing the access of H2O2 to the catalytic site of the enzyme; and direct scavenging of HOCl. Collectively, in addition to acting as an antioxidant and MPO inhibitor, MLT can exert its protective effect by preventing the release of free iron mediated by self-generated HOCl. Our work may establish a direct mechanistic link by which MLT exerts its antioxidant protective effect in chronic inflammatory diseases with MPO elevation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.