ToxSci Advance Access originally published online on July 27, 2005
Toxicological Sciences 2005 87(2):322-327; doi:10.1093/toxsci/kfi266
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
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Effects of PPAR
and Combined Agonists on the Urinary Tract of Rats and Other Species
University of Nebraska Medical Center, Department of Pathology and Microbiology, 983135 Nebraska Medical Center, Omaha, Nebraska 68198–3135
1 For correspondence via fax: (402) 559-9297. E-mail: scohen@unmc.edu.
Received June 16, 2005; accepted July 20, 2005
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INTRODUCTION |
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Peroxisome proliferator-activated receptors (PPAR) are nuclear receptors involved in regulating lipids and the effects of insulin (Yki-Järvinen, 2004
). Three major receptors have been identified, alpha, gamma and delta (beta), with differing tissue distributions and effects. Agonists have been developed for each of these receptors, with differing pharmacologic and toxicologic effects.
PPAR
are present in liver, and also present in several other tissues including skeletal muscle, heart, and brown fat; their agonists have effects on maintenance of lipid levels, especially triglycerides (Klaunig et al., 2003). The toxicological effects of PPAR agonists (peroxisome proliferators) have been extensively investigated, including carcinogenic effects in rodents. They induce liver tumors in rats and mice and frequently induce rat pancreatic acinar cell and testicular Leydig cell tumors. The modes of action for these tumors have been identified and generally been found not to be relevant to humans (at least quantitatively) (Klaunig et al
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DIRECT EFFECT ON PPAR IN THE UROTHELIUM
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INDIRECT MODE OF ACTION INVOLVING URINARY SOLIDS |
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ASSESSMENT OF URINE FOR CHEMICAL CONSTITUENTS AND URINARY SOLIDS |
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EFFECTS ON MONKEY UROTHELIUM |
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SUMMARY AND CONCLUSIONS |
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