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Clioquinol effects on tissue chelatable zinc in mice
Yuval B Nitzan1, Israel Sekler, Christopher J Frederickson
1Department of Morphology, Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Journal of Molecular Medicine (Berlin, Germany)
|August 21, 2003
Summary
Oral clioquinol (CQ) effectively modulates brain zinc levels without affecting key organs, suggesting safety for Alzheimer's disease treatment. Intraperitoneal CQ offers a tool for rapid zinc buffering in neurological emergencies.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Zinc's role in Alzheimer's disease (AD) pathogenesis, specifically beta-amyloid plaque formation, is increasingly evident.
- Metal chelation represents a promising therapeutic strategy for AD.
- Clioquinol (CQ), a membrane-permeable zinc chelator, has shown initial promise in AD mouse models.
Purpose of the Study:
- To investigate the effects of clioquinol (CQ) on chelatable zinc levels in various tissues when administered via oral and intraperitoneal routes.
- To assess the potential therapeutic and clinical applications of CQ based on its impact on zinc homeostasis.
Main Methods:
- Experiments were conducted on a mouse model of Alzheimer's disease.
- Chelatable zinc levels were quantified using 6-methoxy-8-quinolyl- p-toluenesulfonamide (TSQ) histofluorescence and selenite autometalography.
- CQ was administered via two routes: intraperitoneal injection and oral gavage.
Main Results:
- Intraperitoneal CQ administration significantly reduced chelatable zinc in the brain, testis, and pancreas.
- Oral CQ administration did not result in significant changes in chelatable zinc levels in these organs.
- These findings highlight route-dependent effects of CQ on zinc distribution.
Conclusions:
- Oral CQ administration appears safe for long-term use in Alzheimer's disease patients, minimizing risks of zinc deficiency-related adverse effects.
- Intraperitoneal CQ serves as a valuable tool for studying chelatable zinc and has potential clinical applications for rapid zinc buffering after neurological events like ischemia or trauma.
- CQ demonstrates versatility as a scientific and clinical agent for selective modulation of zinc pools.