Melatonin Prevents Myeloperoxidase Heme Destruction and the Generation of Free Iron Mediated by Self-Generated Hypochlorous Acid

Shaeib, Faten; Maitra, Dhiman; Banerjee, Jashoman; Abdulhamid, Ibrahim; Diamond, Michael P.; Saed, Ghassan M.; Pennathur, Subramaniam; Abu-Soûd, Husam M.

doi:10.1016/j.freeradbiomed.2013.10.726

Cited by 2 publications

(4 citation statements)

References 62 publications

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“…Additionally, anti-inflammatory cytokines such as IL-10 increased [ 102 ], and ICAM-1 and MMP9 gene expression was suppressed [ 77 ]. Neutrophil migration and infiltration into the intestinal mucosa are closely associated with myeloperoxidase (MPO) activity, a potent oxidative inducer that catalyzes the production of hypochlorous acid from Cl − and H 2 O 2 in neutrophils [ 112 ]. In line with this, some studies reported reduced colonic MPO levels in animal models of ulcerative colitis after GP consumption [ 78 , 89 , 103 ], with Maurer et al [ 103 ] attributing this response to the fiber-bound (poly)phenols fraction.…”

Section: Effects On Intestinal Inflammatory and Oxidative Statusmentioning

confidence: 99%

Grape Pomace as a Cardiometabolic Health-Promoting Ingredient: Activity in the Intestinal Environment

et al. 2023

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Grape pomace (GP) is a winemaking by-product particularly rich in (poly)phenols and dietary fiber, which are the main active compounds responsible for its health-promoting effects. These components and their metabolites generated at the intestinal level have been shown to play an important role in promoting health locally and systemically. This review focuses on the potential bioactivities of GP in the intestinal environment, which is the primary site of interaction for food components and their biological activities. These mechanisms include (i) regulation of nutrient digestion and absorption (GP has been shown to inhibit enzymes such as α-amylase and α-glucosidase, protease, and lipase, which can help to reduce blood glucose and lipid levels, and to modulate the expression of intestinal transporters, which can also help to regulate nutrient absorption); (ii) modulation of gut hormone levels and satiety (GP stimulates GLP-1, PYY, CCK, ghrelin, and GIP release, which can help to regulate appetite and satiety); (iii) reinforcement of gut morphology (including the crypt-villi structures, which can improve nutrient absorption and protect against intestinal damage); (iv) protection of intestinal barrier integrity (through tight junctions and paracellular transport); (v) modulation of inflammation and oxidative stress triggered by NF-kB and Nrf2 signaling pathways; and (vi) impact on gut microbiota composition and functionality (leading to increased production of SCFAs and decreased production of LPS). The overall effect of GP within the gut environment reinforces the intestinal function as the first line of defense against multiple disorders, including those impacting cardiometabolic health. Future research on GP’s health-promoting properties should consider connections between the gut and other organs, including the gut-heart axis, gut-brain axis, gut-skin axis, and oral-gut axis. Further exploration of these connections, including more human studies, will solidify GP’s role as a cardiometabolic health-promoting ingredient and contribute to the prevention and management of cardiovascular diseases.

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Section: Effects On Intestinal Inflammatory and Oxidative Statusmentioning

confidence: 99%

Grape Pomace as a Cardiometabolic Health-Promoting Ingredient: Activity in the Intestinal Environment

et al. 2023

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“…First, during inflammation when low molecular weight serum ferritin is formed from high molecular weight intracellular ferritin, the latter releases a substantial portion of its inner core iron, which increases the free iron level in the blood [23,24]. Second, inflammation reduces RBC half-life, which leads to macrophage-mediated RBC phagocytosis and eventually, an increase in the free iron in the plasma [25,26]. Third, free iron is also generated from myeloperoxidase (MPO) induced degradation of heme [25].…”

Section: How Is the Iron Acquisition System Of Mucor Species Modified In Covid-19?mentioning

confidence: 99%

“…Second, inflammation reduces RBC half-life, which leads to macrophage-mediated RBC phagocytosis and eventually, an increase in the free iron in the plasma [25,26]. Third, free iron is also generated from myeloperoxidase (MPO) induced degradation of heme [25]. MPO is an enzyme stored in the neutrophils and macrophages and is released into the extracellular fluid during inflammation.…”

Section: How Is the Iron Acquisition System Of Mucor Species Modified In Covid-19?mentioning

confidence: 99%

“…First, melatonin helps in reducing plasma free iron in SARS-COV-2 patients by chelating excess iron (both Fe 2+ and Fe 3+ ) as melatonin is an effective metal chelator [31,32]. Second, melatonin, being a potent anti-inflammatory agent, can help in shrinking the labile iron pool by i) limiting free iron generation from destruction of heme by blocking [25] the enzyme myeloperoxidase (MPO), ii) restricting free iron production from inflammation induced RBC degradation [25,26] and iii) lowering serum ferritin [33,34], which is involved in elevating plasma free iron. Melatonin ameliorates inflammation by blocking pro-inflammatory cytokines such as interleukin IL-1β, IL-2, IL-6, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) [18,19,30,35].…”

Section: How Can Fixing Melatonin Deficiency Restrict Iron Uptake By the Mucor Species?mentioning

confidence: 99%

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Deficient synthesis of melatonin in COVID-19 can impair the resistance of coronavirus patients to mucormycosis

Sen¹

2021

Preprint

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Though it is thought that uncontrolled diabetes and the excessive use of corticosteroids are responsible for COVID-19 associated mucormycosis (CAM), researchers are on the lookout for additional reasons to explain the recent spurt of CAM in India. In the present paper it is argued that melatonin deficiency in COVID-19 plays a major role in CAM. Incidentally, melatonin is synthesized from tryptophan via the serotonin pathway and melatonin deficiency in COVID-19 arises from the faulty absorption of tryptophan from the food because SARS-COV-2 downregulates angiotensin-converting enzyme-2, which is the chaperone of the transporter of tryptophan, a key component in the process of uptake of tryptophan. The melatonin deficiency enhances the fungal virulence by facilitating iron acquisition and by promoting morphological transition of the mucor species from the yeast to the virulent hyphal form. Additionally, melatonin deficiency aggravates the suppression of T-cell immunity in the patients receiving steroids. Hence, the restoration of melatonin level should resolve the issues and help in defeating CAM, given the fact that melatonin is an iron chelator, inhibitor of myeloperoxidase, inhibitor of ferroptosis and pyroptosis and calmodulin blocker. Also, by lowering the expression of glucose-regulated protein-78, melatonin can further increase the resistance of diabetic patients to mucormycosis. Hence, clinical trials should be carried out to ascertain how tryptophan supplementation, administration of selective serotonin reuptake inhibitors (to increase serotonin, the precursor of melatonin), and exogenous melatonin help in correcting the melatonin deficiency and eliminating or reducing the propensity of the patients to CAM.

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Melatonin Prevents Myeloperoxidase Heme Destruction and the Generation of Free Iron Mediated by Self-Generated Hypochlorous Acid

Cited by 2 publications

References 62 publications

Grape Pomace as a Cardiometabolic Health-Promoting Ingredient: Activity in the Intestinal Environment

Grape Pomace as a Cardiometabolic Health-Promoting Ingredient: Activity in the Intestinal Environment

Deficient synthesis of melatonin in COVID-19 can impair the resistance of coronavirus patients to mucormycosis

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