Acrodermatitis enteropathica treated by zinc

Portnoy, Benjamin; Molokhia, Mohamed M.

doi:10.1111/j.1365-2133.1974.tb12458.x

Cited by 26 publications

(5 citation statements)

References 7 publications

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“…It can be corrected by oral zinc supplements. In untreated patients with the disease the plasma zinc concentration is usually abnormally low (Michaelsson 1974;Moynahan 1974;Portnoy and Molokhia 1974;NeIder and Hambidge 1975), but this is not a universal finding (Garretts and Molokhia 1977). Abnormally low amounts of zinc in urine (NeIder and Hambidge 1975) and hair (Amador et al 1975) have also been reported.…”

Section: Inherited Disorders Of Zinc Metabolismmentioning

confidence: 92%

Physiology of Zinc: General Aspects

Jackson¹

1989

ILSI Human Nutrition Reviews

150

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Section: Inherited Disorders Of Zinc Metabolismmentioning

confidence: 92%

Physiology of Zinc: General Aspects

Jackson¹

1989

ILSI Human Nutrition Reviews

150

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“…Because CQ and PBT2 appear to redistribute metals into cells, these compounds have more recently been characterized as copper and zinc ionophores. − In AD, copper and zinc redistribution into deficient neurons is thought to trigger a signaling pathway that results in reduced amyloid β levels in the brain and improved cognition. , In cancers, redistribution of copper, zinc, and iron into cancer cells is thought to trigger toxic metal ion accumulation, which then results in cancer cell death. ,− In addition, this ionophoric character of 8HQs may explain the effectiveness of 8HQ treatment in other metal-linked diseases such as acrodermatitis enteropathica, a lethal inherited human zinc-deficiency disorder. − …”

Section: Introductionmentioning

confidence: 99%

Solution Chemistry of Copper(II) Binding to Substituted 8-Hydroxyquinolines

et al. 2020

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8-Hydroxyquinolines (8HQs) are a family of lipophilic metal ion chelators that have been used in a range of analytical and pharmaceutical applications over the last 100 years. More recently, CQ (clioquinol; 5-chloro-7-iodo-8-hydroxyquinoline) and PBT2 (5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline) have undergone clinical trials for the treatment of Alzheimer's disease and Huntington's disease. Because CQ and PBT2 appear to redistribute metals into cells, these compounds have been redefined as copper and zinc ionophores. Despite the attention surrounding the clinical trials and the clear link between 8HQs and metals, the fundamental solution chemistry of how these compounds bind divalent metals such as copper and zinc, as well as their mechanism(s) of action in mammalian systems, remains poorly understood. In this study, we used a combination of X-ray absorption spectroscopy (XAS), high-energy resolution fluorescence detected (HERFD) XAS, electron paramagnetic resonance (EPR), and UV−visible absorption spectroscopies to investigate the aqueous solution chemistry of a range of 8HQ derivatives. To circumvent the known solubility issues with 8HQ compounds and their complexes with Cu(II), and to avoid the use of abiological organic solvents, we have devised a surfactant buffer system to investigate these Cu(II) complexes in aqueous solution. Our study comprises the first comprehensive investigation of the Cu(II) complexes formed with many 8HQs of interest in aqueous solution, and it provides the first structural information on some of these complexes. We find that halogen substitutions in 8HQ derivatives appear to have little effect on the Cu(II) coordination environment; 5,7-dihalogenated 8HQ conformers all have a pseudo square planar Cu(II) bound by two quinolin-8-olate anions, in agreement with previous studies. Conversely, substituents in the 2-position of the 8HQ moiety appear to cause significant distortions from the typical square-planar-like coordination of most Cu(II)-bis-8HQ complexes, such that the 8HQ moieties in the Cu(II)-bis-8HQ complex are rotated approximately 30−40°apart in a "propeller-like" arrangement.

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“…It was later discovered that this was a genetically determined disorder of zinc metabolism, resulting in a decreased ability to absorb zinc from the intestine (Moynahan 1974). It was then suggested that the efficacy of 5,7diiodo-8-hydroxy-quinoline might be related to the formation of an absorbable zinc-chelate (Portnoy & Molokhia 1974). Increased plasma levels of 65Zn induced by clioquinol have been shown in calves with Adema disease, which is the bovine parallel to acrodermatitis enteropathica (Flagstad 1977).…”

mentioning

confidence: 99%

Effect of 5‐Chloro‐7‐iodo‐8‐hydroxy‐quinoline (Clioquinol) on the Uptake and Distribution of Nickel, Zinc and Mercury in Mice

Tjälve

Ståhl

1984

Acta Pharmacologica et Toxicologica

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5‐Chloro‐7‐iodo‐8‐hydroxy‐quinoline (clioquinol) was found to induce a very marked increase in the concentration of 63Ni2+ in various tissues of mice when given orally together with the metal, compared with oral administrations of 63Ni2+ only. Markedly increased tissue concentrations, although less expressed than for the 63Ni2+, were also observed for 65Zn2+. Clioquinol increased the tissue levels of 203Hg2+ to a lesser extent. When clioquinol was given intraperitoneally and 63Ni2+ was given intravenously there were also very markedly increased tissue levels of the metal, compared with intravenous injections of 63Ni2+ only. It was also shown that the urinary excretion of 63Ni2+ was greatly increased in mice given the metal orally together with clioquinol, compared with mice given the 63Ni2+ only. Clioquinol and other 8‐hydroxy‐quinolines form lipophilic chelates with metallic cations and the observed effects on the tissue‐disposition of the metals are probably due to a facilitated penetration through the cellular membranes. Determinations of the chloroform:water partition coefficients showed the highest lipophilicity for the nickel‐clioquinol‐complex followed in decreasing order by the complexes with zinc and mercury. These data suggest that the ability of the clioquinol to affect the uptake of the metals in the cells may be related to the relative lipophilicity of the metal‐clioquinol‐complexes. Clioquinol and other halogenated 8‐hydroxy‐quinolines are linked with the SMON‐syndrom, which has been observed preferentially in Japan. It is suggested that the pathogenesis of SMON may involve an accumulation of toxic concentrations of metals in the tissues due to facilitated uptake by complex‐formation with halogenated 8‐hydroxy‐quinolines. The Japanese have been more heavily exposed to metals by environmental pollution than most people in other countries, explaining the prevalent occurrence of SMON in Japan.

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Acrodermatitis enteropathica treated by zinc

Abstract: SUMMARY A case of acrodermatitis enteropathica has, after 14 years essential treatment with Diodoquin, been able to abandon this therapy on exhibition of zinc.

Cited by 26 publications

References 7 publications

Physiology of Zinc: General Aspects

Physiology of Zinc: General Aspects

Solution Chemistry of Copper(II) Binding to Substituted 8-Hydroxyquinolines

Effect of 5‐Chloro‐7‐iodo‐8‐hydroxy‐quinoline (Clioquinol) on the Uptake and Distribution of Nickel, Zinc and Mercury in Mice

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