Pro-oxidant activity of aluminum: Promoting the Fenton reaction by reducing Fe(III) to Fe(II)

Ruipérez, Fernando; Mujika, Jon I.; Ugalde, Jesus M.; Exley, Christopher; López, Xabier

doi:10.1016/j.jinorgbio.2012.09.008

Cited by 112 publications

(87 citation statements)

References 77 publications

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“…Al 3+ does not on its own effect Fenton chemistry; however, under conditions where there might be iron present (as will be the case in PRP of healthy individuals) it can actually contribute to Fenton chemistry. 414,415 Overall, these observations (and literature) are consistent with the view that a great many substances can have substantial effects on the rate of fibrinogen polymerisation and on the nature and structure of the fibres and clots formed. In some senses, fibrin structure might be considered to be a kind of bellwether of plasma health.…”

supporting

confidence: 85%

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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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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supporting

confidence: 85%

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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“…Al 3+ toxicity has correlates with pro-oxidant activity in several organs and tissues [40,26,41,42], and more recently in male reproductive toxicity [11,18,19]. In the present study, Al exposure increased oxidative stress in testis, epididymis and prostate, as evident from an increase in RS generation and MDA levels.…”

Section: Discussionsupporting

confidence: 62%

Aluminum exposure for 60 days at human dietary levels impairs spermatogenesis and sperm quality in rats

Martinez

Escobar

Uranga

et al. 2017

Reproductive Toxicology

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Highlights Our study shows that 60-day exposure to low doses of aluminum, which aimed to mimic human exposure to dietary aluminum is able to impair male reproductive health. Strikingly, the reproductive impairment was, sometimes, less-marked at the higher dose of Al, raising concerns regard to safe values for human exposure to aluminum. AbstractConcerns about environmental aluminum (Al) and reproductive health have been raised. We investigated the effects of Al exposure at a human relevant dietary level and a high level exposure to Al. Experiment 1 (Lower level) rats were treated orally for 60 days: a) controls -ultrapure water; b) aluminum at 1.5 mg/kg bw/day and c) aluminum at 8.3 mg/kg bw/day. Experiment 2 (High level) rats were treated for 42 days: a) controls -ultrapure water; b) aluminum at 100 mg/kg bw/day. Al decreased sperm count, daily sperm production, sperm motility, normal morphological sperm, impaired testis histology; increased oxidative stress in reproductive organs and inflammation in testis. Our study shows the specific presence of Al in the germinative cells and, that low concentrations of Al in testes (3.35 μg/g) are sufficient to impair spermatogenesis and sperm quality. Our findings provide a better understanding of the reproductive health risk of Al.

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“…Al has been detected in amyloid fibers in the cores of senile plaques in brains of AD patients [22]. The presence of Al in biological systems could lead to an important prooxidant activity, by promoting superoxide generation through Fenton reaction [23]. More recently, Al removal in AD patients by treatment with DFO has been further proposed [24].…”

Section: Discussionmentioning

confidence: 99%

Aluminium Involvement in Neurotoxicity

Fulgenzi

Vietti

Ferrero

2014

BioMed Research International

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The aetiology of neurodegenerative diseases (ND) seems to involve susceptibility genes and environmental factors. Toxic metals are considered major environmental pollutants. Following our study of a case of multiple sclerosis (MS) improvement due to removal of aluminium (Al) and other toxic metals, we have examined the possible relationship between Al intoxication and ND. We used the slow intravenous treatment with the chelating agent EDTA (calcium disodium ethylene diamine tetraacetic acid) (chelation test) to remove Al and detected it in the urine collected from the patients for 12 hours. Patients affected by MS represented 85.6% of total ND. Al was present in 44.8% of cases comprehensive of ND and healthy patients. Al levels were significantly higher in ND patients than in healthy subjects. We here show that treatment of patients affected by Al burden with ten EDTA chelation therapies (EDTA intravenous administration once a week) was able to significantly reduce Al intoxication.

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Pro-oxidant activity of aluminum: Promoting the Fenton reaction by reducing Fe(III) to Fe(II)

Cited by 112 publications

References 77 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)

Aluminum exposure for 60 days at human dietary levels impairs spermatogenesis and sperm quality in rats

Aluminium Involvement in Neurotoxicity

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