Clioquinol synergistically augments rescue by zinc supplementation in a mouse model of acrodermatitis enteropathica.

<h4>Background</h4>Zinc deficiency due to poor nutrition or genetic mutations in zinc transporters is a global health problem and approaches to providing effective dietary zinc supplementation while avoiding potential toxic side effects are needed.<h4>Methods/principal findings<...

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Autores principales:	Jim Geiser, Robert C De Lisle, David Finkelstein, Paul A Adlard, Ashley I Bush, Glen K Andrews
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/83a06b4ef9494a5aab94221ac8aff609
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spelling	oai:doaj.org-article:83a06b4ef9494a5aab94221ac8aff6092021-11-18T08:57:52ZClioquinol synergistically augments rescue by zinc supplementation in a mouse model of acrodermatitis enteropathica.1932-620310.1371/journal.pone.0072543https://doaj.org/article/83a06b4ef9494a5aab94221ac8aff6092013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24015258/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Zinc deficiency due to poor nutrition or genetic mutations in zinc transporters is a global health problem and approaches to providing effective dietary zinc supplementation while avoiding potential toxic side effects are needed.<h4>Methods/principal findings</h4>Conditional knockout of the intestinal zinc transporter Zip4 (Slc39a4) in mice creates a model of the lethal human genetic disease acrodermatitis enteropathica (AE). This knockout leads to acute zinc deficiency resulting in rapid weight loss, disrupted intestine integrity and eventually lethality, and therefore provides a model system in which to examine novel approaches to zinc supplementation. We examined the efficacy of dietary clioquinol (CQ), a well characterized zinc chelator/ionophore, in rescuing the Zip4 (intest KO) phenotype. By 8 days after initiation of the knockout neither dietary CQ nor zinc supplementation in the drinking water was found to be effective at improving this phenotype. In contrast, dietary CQ in conjunction with zinc supplementation was highly effective. Dietary CQ with zinc supplementation rapidly restored intestine stem cell division and differentiation of secretory and the absorptive cells. These changes were accompanied by rapid growth and dramatically increased longevity in the majority of mice, as well as the apparent restoration of the homeostasis of several essential metals in the liver.<h4>Conclusions</h4>These studies suggest that oral CQ (or other 8-hydroxyquinolines) coupled with zinc supplementation could provide a facile approach toward treating zinc deficiency in humans by stimulating stem cell proliferation and differentiation of intestinal epithelial cells.Jim GeiserRobert C De LisleDavid FinkelsteinPaul A AdlardAshley I BushGlen K AndrewsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72543 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jim Geiser Robert C De Lisle David Finkelstein Paul A Adlard Ashley I Bush Glen K Andrews Clioquinol synergistically augments rescue by zinc supplementation in a mouse model of acrodermatitis enteropathica.
description	<h4>Background</h4>Zinc deficiency due to poor nutrition or genetic mutations in zinc transporters is a global health problem and approaches to providing effective dietary zinc supplementation while avoiding potential toxic side effects are needed.<h4>Methods/principal findings</h4>Conditional knockout of the intestinal zinc transporter Zip4 (Slc39a4) in mice creates a model of the lethal human genetic disease acrodermatitis enteropathica (AE). This knockout leads to acute zinc deficiency resulting in rapid weight loss, disrupted intestine integrity and eventually lethality, and therefore provides a model system in which to examine novel approaches to zinc supplementation. We examined the efficacy of dietary clioquinol (CQ), a well characterized zinc chelator/ionophore, in rescuing the Zip4 (intest KO) phenotype. By 8 days after initiation of the knockout neither dietary CQ nor zinc supplementation in the drinking water was found to be effective at improving this phenotype. In contrast, dietary CQ in conjunction with zinc supplementation was highly effective. Dietary CQ with zinc supplementation rapidly restored intestine stem cell division and differentiation of secretory and the absorptive cells. These changes were accompanied by rapid growth and dramatically increased longevity in the majority of mice, as well as the apparent restoration of the homeostasis of several essential metals in the liver.<h4>Conclusions</h4>These studies suggest that oral CQ (or other 8-hydroxyquinolines) coupled with zinc supplementation could provide a facile approach toward treating zinc deficiency in humans by stimulating stem cell proliferation and differentiation of intestinal epithelial cells.
format	article
author	Jim Geiser Robert C De Lisle David Finkelstein Paul A Adlard Ashley I Bush Glen K Andrews
author_facet	Jim Geiser Robert C De Lisle David Finkelstein Paul A Adlard Ashley I Bush Glen K Andrews
author_sort	Jim Geiser
title	Clioquinol synergistically augments rescue by zinc supplementation in a mouse model of acrodermatitis enteropathica.
title_short	Clioquinol synergistically augments rescue by zinc supplementation in a mouse model of acrodermatitis enteropathica.
title_full	Clioquinol synergistically augments rescue by zinc supplementation in a mouse model of acrodermatitis enteropathica.
title_fullStr	Clioquinol synergistically augments rescue by zinc supplementation in a mouse model of acrodermatitis enteropathica.
title_full_unstemmed	Clioquinol synergistically augments rescue by zinc supplementation in a mouse model of acrodermatitis enteropathica.
title_sort	clioquinol synergistically augments rescue by zinc supplementation in a mouse model of acrodermatitis enteropathica.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/83a06b4ef9494a5aab94221ac8aff609
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Clioquinol synergistically augments rescue by zinc supplementation in a mouse model of acrodermatitis enteropathica.

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