Current Biomedical Use of Copper Chelation Therapy

Baldari, Silvia; Rocco, Giuliana Di; Toietta, Gabriele

doi:10.3390/ijms21031069

Cited by 114 publications

(114 citation statements)

References 176 publications

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“…Chelation therapy has shown promise in the diseases including AD, PD, autism, cancer, cardiovascular disease, etc. [269,270]. Chelating agents not only reduces raised metal concentration but some thiol based chelators, such as meso 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropane 1-sulfonate (DMPS), D-pencillamine (DPA), and Monoisoamyldimercaptosuccinic acid (MiADMSA) ( Table 6) also have ROS neutralizing ability that can additionally diminish the augmented oxidative stress and further preventing cellular damage from oxidative insult [271].…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

Patwa

Flora

2020

IJMS

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Heavy metals are considered a continuous threat to humanity, as they cannot be eradicated. Prolonged exposure to heavy metals/metalloids in humans has been associated with several health risks, including neurodegeneration, vascular dysfunction, metabolic disorders, cancer, etc. Small blood vessels are highly vulnerable to heavy metals as they are directly exposed to the blood circulatory system, which has comparatively higher concentration of heavy metals than other organs. Cerebral small vessel disease (CSVD) is an umbrella term used to describe various pathological processes that affect the cerebral small blood vessels and is accepted as a primary contributor in associated disorders, such as dementia, cognitive disabilities, mood disorder, and ischemic, as well as a hemorrhagic stroke. In this review, we discuss the possible implication of heavy metals/metalloid exposure in CSVD and its associated disorders based on in-vitro, preclinical, and clinical evidences. We briefly discuss the CSVD, prevalence, epidemiology, and risk factors for development such as genetic, traditional, and environmental factors. Toxic effects of specific heavy metal/metalloid intoxication (As, Cd, Pb, Hg, and Cu) in the small vessel associated endothelium and vascular dysfunction too have been reviewed. An attempt has been made to highlight the possible molecular mechanism involved in the pathophysiology, such as oxidative stress, inflammatory pathway, matrix metalloproteinases (MMPs) expression, and amyloid angiopathy in the CSVD and related disorders. Finally, we discussed the role of cellular antioxidant defense enzymes to neutralize the toxic effect, and also highlighted the potential reversal strategies to combat heavy metal-induced vascular changes. In conclusion, heavy metals in small vessels are strongly associated with the development as well as the progression of CSVD. Chelation therapy may be an effective strategy to reduce the toxic metal load and the associated complications.

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Section: Therapeutic Strategiesmentioning

confidence: 99%

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

Patwa

Flora

2020

IJMS

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“…Different mechanisms are involved in copper drugs’ anticancer effect. They act as chelators, and interact with and sequester endogenous copper, reducing its availability for tumor growth and angiogenesis [ 39 ]. On the contrary, ionophores trigger intracellular copper accumulation, cytotoxicity, and activate apoptosis inhibitor factor (XIAP) [ 24 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ].…”

Section: Introductionmentioning

confidence: 99%

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

Molinaro

Martoriati

Pélinski

et al. 2020

Cancers

115

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Organometallics, such as copper compounds, are cancer chemotherapeutics used alone or in combination with other drugs. One small group of copper complexes exerts an effective inhibitory action on topoisomerases, which participate in the regulation of DNA topology. Copper complexes inhibitors of topoisomerases 1 and 2 work by different molecular mechanisms, analyzed herein. They allow genesis of DNA breaks after the formation of a ternary complex, or act in a catalytic mode, often display DNA intercalative properties and ROS production, and sometimes display dual effects. These amplified actions have repercussions on the cell cycle checkpoints and death effectors. Copper complexes of topoisomerase inhibitors are analyzed in a broader synthetic view and in the context of cancer cell mutations. Finally, new emerging treatment aspects are depicted to encourage the expansion of this family of highly active anticancer drugs and to expend their use in clinical trials and future cancer therapy.

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“…Increased Cu concentration is associated with damages, including neurotoxicity [ 22 ] and neurological conditions such as Alzheimer's disease (AD), [ 23,24 ] Parkinson's disease, Menke's disease, Wilson's disease, and so forth. [ 1,11,25,26 ] For instance, studies revealed that Cu imbalance has widely affected the functions of neurons and may lead to cognitive deficits and AD pathology. [ 27 ] Also, it has been established that Cu accumulates in the amyloid β plaque of patients with AD.…”

Section: Introductionmentioning

confidence: 99%

Rutin ameliorates copper sulfate‐induced brain damage via antioxidative and anti‐inflammatory activities in rats

Arowoogun

Akanni

Adefisan

et al. 2020

J Biochem & Molecular Tox

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Excessive exposure to Copper (Cu) may result in Cu toxicity and adversely affect health outcomes. We investigated the protective role of rutin on Cu‐induced brain damage. Experimental rats were treated as follows: group I: control; group II: Cu‐sulfate: 200 mg/kg; group III: Cu‐sulfate, and rutin 100 mg/kg; and group IV: rutin 100 mg/kg, for 7 weeks. Cu only treatment significantly decreased body weight gain, while rutin cotreatment reversed this decrease. Cu treatment increased malondialdehyde, nitric oxide level, and myeloperoxidase activity and decreased superoxide dismutase and catalase activities in rat brain. Immunohistochemistry showed that COX‐2, iNOS, and Bcl‐2 proteins were strongly expressed, while Bax was mildly expressed in the brain of Cu‐treated rats. Furthermore, brain histology revealed degenerated neurons, and perforated laminae of cerebral cortex in the Cu‐only treated rats. Interestingly, coadministration of Cu and rutin reduced the observed histological alteration, improved inflammatory and antioxidant biomarkers, thereby protecting against Cu‐induced brain damage via antioxidative and anti‐inflammatory mechanisms.

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Current Biomedical Use of Copper Chelation Therapy

Cited by 114 publications

References 176 publications

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

Rutin ameliorates copper sulfate‐induced brain damage via antioxidative and anti‐inflammatory activities in rats

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