The protection conferred by chelation therapy in post-MI diabetics might be replicated by high-dose zinc supplementation☆
Section snippets
Chelation therapy decreases vascular events in diabetics – a role for AGE reduction?
IN the Trial to Assess Chelation Therapy (TACT), subjects who had previously experienced a myocardial infarction were randomized to receive intravenous EDTA or placebo solutions 40 times over approximately one year, and were followed for five years; primary endpoints assessed were death, re-infarction, stroke, coronary revascularization, or hospitalization for angina [1]. Somewhat surprisingly, a major reduction in the primary endpoints was observed in the 633 diabetic subjects (hazard ratio
Copper, rather than iron, may be the key target of chelation therapy
If this formulation is essentially correct, is either iron or copper the primary culprit whose removal was protective in the TACT study? A previous study may cast some light on this issue. The Iron and Atherosclerosis Study (FeAST) randomized 1277 patients with stable symptomatic peripheral arterial disease to a control group or a group receiving repeated phlebotomies [6]. In treated patients who were reasonably compliant, baseline ferritin levels were reduced by approximately half, whereas
Supplemental zinc, via metallothionein induction, prevents diabetic complications
What alternative strategies might be feasible? It is well known that high intakes of supplemental zinc can be employed in the treatment of Wilson’s disease (often as maintenance therapy after an initial course of trientine), owing to the fact that high-dose zinc promotes induction of the protein metallothionein [21], [22], [23], [24]. This protein, an antioxidant rich in cysteine groups, binds not only to zinc, but also copper and cadmium; in this bound form, copper and cadmium are innocuous.
Alternative copper chelators – focus on histidine
A number of agents – drugs and natural metabolites – have moderate affinity for copper, and their copper chelates have limited redox activity. Although these agents do not boost urinary loss of copper as trientine does, they have the potential to compete for the loosely bound copper affiliated with AGE-modified proteins, and hence may render this copper less pathogenic [2], [76], [77]. Baynes and colleagues have noted that a number of commonly used drugs can suppress copper-catalyzed oxidation
A caution on vitamin C
If labile extracellular copper does indeed increase risk for mortality and cardiovascular events in diabetics, then it is reasonable to suspect that chemical agents capable of reducing this copper to its cuprous superoxide-generating form could exacerbate its pathogenicity. In this regard, vitamin C comes to mind, as it readily reduces free copper and iron [90]. (This is the basis of the utility of mega-dose intravenous ascorbate in cancer therapy [91], [92]). Indeed, some practitioners of
Conflict of interest
The authors have no conflicts of interest.
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Dyslipdemia induced by chronic low dose co-exposure to lead, cadmium and manganese in rats: the role of oxidative stress
2017, Environmental Toxicology and PharmacologyCitation Excerpt :The antioxidant property of MTs has been elucidated by Helal and Helal (2009), who showed that MTs reduce oxidative stress in rats. Zinc protects cell membranes from oxidative damage, is normally bound to MTs (Krizkova et al., 2010), and is suggested to boost antioxidant MT protein expression via antagonism to redox activity (McCarty and DiNicolantinio, 2015). In the current study, the reduction in serum Zn concentration corresponds well with the lowered levels of MT1 in the metal treatment groups.
Role of Trientine in Hypertrophic Cardiomyopathy: A Review of Mechanistic Aspects
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2016, Archives of Toxicology
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