| Suppressive effects of acid-forming diet against the tumorigenic potential of pioglitazone hydrochloride in the urinary bladder of male rats. | |
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MedLine Citation:
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PMID: 21255596 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Pioglitazone hydrochloride (PIO), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, was administered orally for 85weeks at 16mg/kg/day to male rats fed either a diet containing 1.5% ammonium chloride (acid-forming diet) or a control diet to investigate the effects of urinary acidification induced by the acid-forming diet on the tumorigenic potential of PIO in the urinary bladder. The surviving animals at the end of the administration period were followed to the end of the 2-year study period without changes in the diet and were subjected to terminal necropsy on Week 104. The number of urinary microcrystals, evaluated by manual counting with light microscopy and by an objective method with a laser diffraction particle size analyzer, was increased by PIO on Weeks 12 and 25 and the increases were markedly suppressed by urinary acidification. Urinary citrate was decreased by PIO throughout the study period, but no changes were seen in urinary oxalate at any timepoint. The incidences of PIO-treated males bearing at least one of the advanced proliferative changes consisting of papillary hyperplasia, nodular hyperplasia, papilloma or carcinoma were significantly decreased from 11 of 82 males fed the control diet to 2 of 80 males fed the acid-forming diet. The acid-forming diet did not show any effects on the toxicokinetic parameters of PIO and its metabolites. Microcrystalluria appears to be involved in the development of the advanced stage proliferative lesions in bladder tumorigenesis induced by PIO in male rats. |
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Authors:
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Keiichiro Sato; Yasuyuki Awasaki; Hitoshi Kandori; Zen-Yo Tanakamaru; Hirofumi Nagai; David Baron; Masaki Yamamoto |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-19 |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: - ISSN: 1096-0333 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Inc. |
Affiliation:
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Development Research Center, Takeda Pharmaceutical Company Limited, Osaka 532-8686, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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