Pharmaceutical & toxicological investigations of metals: investigations of supplemental chromium(iii) and iron oxide nanoparticles in rodent models

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dc.contributor Earley, Ryan L.
dc.contributor O'Donnell, Janis M.
dc.contributor Ramonell, Katrina M.
dc.contributor Vincent, John B.
dc.contributor.advisor Rasco, Jane F.
dc.contributor.author Di Bona, Kristin Rogers
dc.date.accessioned 2017-03-01T17:22:02Z
dc.date.available 2017-03-01T17:22:02Z
dc.date.issued 2014
dc.identifier.other u0015_0000001_0001804
dc.identifier.other DiBona_alatus_0004D_12119
dc.identifier.uri https://ir.ua.edu/handle/123456789/2248
dc.description Electronic Thesis or Dissertation
dc.description.abstract Trivalent chromium (Cr^3+) has widely been accepted as a nutritional element necessary for proper carbohydrate and lipid metabolism in mammals. Upon closer examination, beneficial effects resulting from Cr supplementation in many rodent studies are actually pharmaceutical in nature due in part to additional stressors and supranutritional doses. Zucker lean, obese (ZOB), and diabetic fatty (ZDF) rats were used to examine the effects of Cr supplementation on healthy and insulin-resistant models of type 2 diabetes and pre-diabetes, respectively. Increased insulin sensitivity was observed in Zucker lean rats receiving a highly Cr-supplemented diet (+1,000 μg Cr/kg diet), although urinary Cr levels did not correlate with supplementation. ZDF rats displayed both increased absorption and increased urinary excretion of ^51 Cr when given a single ^51 CrCl_3 dose. With extended Cr supplementation, elevated kidney Cu levels in the ZDF rats decreased in the highest CrCl_3 and Cr3 treatments (1,000 μg Cr/kg body mass). Nanoparticles (NPs) are widely being explored for use in biomedicine. One concern with the increased prevalence and availability of pharmaceutical NPs is the potential developmental toxicity that may result from exposure in utero. Due in part to their small size, NPs may have the ability to cross the placenta and accumulate in the fetus. Iron oxide NPs are currently being used as supplements for patients with Fe deficiencies as well as contrast agents for magnetic resonance imaging. In order to aid in a more "intelligent design" of NPs to which pregnant women may be exposed, the developmental toxicity of surface-charged iron oxide NPs was investigated in CD-1 mice in order to determine whether iron oxide NPs cross the placenta and accumulate in the fetus and whether the surface-charge influences toxicity. Pregnant CD-1 mice were exposed to 1 or 8 doses of 10 mg NPs/kg body mass, the equivalent of one MRI exposure. Exposure to positively-charged polyethylenimine-coated NPs resulted in greater toxicity compared to controls or negatively-charged poly(acrylic acid)-coated NPs, exhibiting increased fetal resorptions, decreased maternal weight gain, and increased Fe accumulation in the fetal liver.
dc.format.extent 160 p.
dc.format.medium electronic
dc.format.mimetype application/pdf
dc.language English
dc.language.iso en_US
dc.publisher University of Alabama Libraries
dc.relation.ispartof The University of Alabama Electronic Theses and Dissertations
dc.relation.ispartof The University of Alabama Libraries Digital Collections
dc.relation.hasversion born digital
dc.rights All rights reserved by the author unless otherwise indicated.
dc.subject.other Biochemistry
dc.subject.other Developmental biology
dc.subject.other Pharmacology
dc.title Pharmaceutical & toxicological investigations of metals: investigations of supplemental chromium(iii) and iron oxide nanoparticles in rodent models
dc.type thesis
dc.type text
etdms.degree.department University of Alabama. Dept. of Biological Sciences
etdms.degree.discipline Biological Sciences
etdms.degree.grantor The University of Alabama
etdms.degree.level doctoral
etdms.degree.name Ph.D.


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