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

Posted on:2015-07-04Degree:Ph.DType:Dissertation
University:The University of AlabamaCandidate:Di Bona, Kristin RogersFull Text:PDF
GTID:1471390017994107Subject:Biochemistry
Abstract/Summary:
Trivalent chromium (Cr3+) 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 mug Cr/kg diet), although urinary Cr levels did not correlate with supplementation. ZDF rats displayed both increased absorption and increased urinary excretion of 51Cr when given a single 51CrCl3 dose. With extended Cr supplementation, elevated kidney Cu levels in the ZDF rats decreased in the highest CrCl3 and Cr3 treatments (1,000 mug 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.
Keywords/Search Tags:Iron oxide, Nps, Increased, Pharmaceutical
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