The hazards of iron loading

Although the two phenomena are usually studied separately, we summarise a considerable body of literature to the effect that a great many diseases involve (or are accompanied by) both an increased tendency for blood to clot (hypercoagulability) and the resistance of the clots so formed (hypofibrinolysis) to the typical, 'healthy' or physiological lysis. We concentrate here on the terminal stages of fibrin formation from fibrinogen, as catalysed by thrombin. Hypercoagulability goes hand in hand with inflammation, and is strongly influenced by the fibrinogen concentration (and vice versa); this can be mediated via interleukin-6. Poorly liganded iron is a significant feature of inflammatory diseases, and hypofibrinolysis may change as a result of changes in the structure and morphology of the clot, which may be mimicked in vitro, and may be caused in vivo, by the presence of unliganded iron interacting with fibrin(ogen) during clot formation. Many of these phenomena are probably caused by electrostatic changes in the iron-fibrinogen system, though hydroxyl radical (OH ) formation can also contribute under both acute and (more especially) chronic conditions. Many substances are known to affect the nature of fibrin polymerised from fibrinogen, such that this might be seen as a kind of bellwether for human or plasma health. Overall, our analysis demonstrates the commonalities underpinning a variety of pathologies as seen in both hypercoagulability and hypofibrinolysis, and offers opportunities for both diagnostics and therapies.

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“…ref. [80][81][82][83][84][85] are also those in which a hypercoagulable and/or hypofibrinolytic state may be observed.…”

Section: Relationship Between Chronic Inflammation and Hypercoagulabimentioning

confidence: 99%

The simultaneous occurrence of both hypercoagulability and hypofibrinolysis in blood and serum during systemic inflammation, and the roles of iron and fibrin(ogen)

Kell

Pretorius

2014

Integrative Biology

127

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“…In addition to the innate immune system and the adaptive (acquired) immune system, to which both of the aforementioned lymphocyte classes belong, a mechanism called ‘nutritional immunity' [39,40] comes into play in the context of nutrients, their deficiency and regulatory responses. This phenomenon arises with nutrients that are essential both to potential pathogens and to the hosts.…”

Section: Zinc Immunity and Host Defenses Against Pathogensmentioning

confidence: 99%

Update on Zinc Biology

Solomons¹

2013

Ann Nutr Metab

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Zinc has become a prominent nutrient of clinical and public health interest in the new millennium. Functions and actions for zinc emerge as increasingly ubiquitous in mammalian anatomy, physiology and metabolism. There is undoubtedly an underpinning in fundamental biology for all of the aspects of zinc in human health (clinical and epidemiological) in pediatric and public health practice. Unfortunately, basic science research may not have achieved a full understanding as yet. As a complement to the applied themes in the companion articles, a selection of recent advances in the domains homeostatic regulation and transport of zinc is presented; they are integrated, in turn, with findings on genetic expression, intracellular signaling, immunity and host defense, and bone growth. The elements include ionic zinc, zinc transporters, metallothioneins, zinc metalloenzymes and zinc finger proteins. In emerging basic research, we find some plausible mechanistic explanations for delayed linear growth with zinc deficiency and increased infectious disease resistance with zinc supplementation.

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“…It is known that excessive iron deposition in the body injures various organs including the liver (Papanikolaou and Pantopoulos, 2005;Weinberg, 2010), and it has been reported that a relationship exists between hepatic iron deposition and disease progression in NAFLD/NASH patients (Sumida et al, 2009;Nelson et al, 2012). Because several studies have indicated that a relationship exists between lipid metabolism and iron metabolism, we assumed that a cholesterol-lowering agent could potentially influence iron metabolism.…”

Section: Discussionmentioning

confidence: 99%

Ezetimibe Increases Hepatic Iron Levels in Mice Fed a High-Fat Diet

Kishino

Tanaka

Ikeda

et al. 2013

The Journal of Pharmacology and Experimental Therapeutics

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Accumulating evidence suggests that ezetimibe may be a promising agent for treatment of nonalcoholic fatty liver disease and steatohepatitis (NAFLD/NASH). Phlebotomy and dietary iron restriction reduce serum transaminase in NAFLD/NASH patients. Recent studies have shown that a mutual effect exists between lipid metabolism and iron metabolism. Accordingly, we examined the effect of ezetimibe on iron metabolism in mice fed a high-fat diet with or without iron. We fed C57BL/6 mice the following diets for 12 weeks. and duodenum were removed after 12 weeks. In experiment 1, the hepatic iron levels were higher in HE than H, whereas there was no difference between C and CE. Hepatic mRNA expression of transferrin receptor 1 and 2, ferritins, and hepcidin were increased more in CE than C, and more in HE than H. In the duodenum, divalent metal transporter 1, ferritin H, and hephaestin mRNA levels were increased in CE compared with C. In experiment 2, hepatic iron concentrations were higher in HIE than HI. Hepatic mRNA expression of ferritin L and hepcidin were increased in HIE compared with HI. In duodenum, ferritin L mRNA was increased in HIE compared with CIE. Ezetimibe induced hepatic iron uptake transporter expression in mice fed a high-fat diet, causing increased hepatic iron concentrations.

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The hazards of iron loading

Cited by 85 publications

References 147 publications

The simultaneous occurrence of both hypercoagulability and hypofibrinolysis in blood and serum during systemic inflammation, and the roles of iron and fibrin(ogen)

The simultaneous occurrence of both hypercoagulability and hypofibrinolysis in blood and serum during systemic inflammation, and the roles of iron and fibrin(ogen)

Update on Zinc Biology

Ezetimibe Increases Hepatic Iron Levels in Mice Fed a High-Fat Diet

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