help button home button Am J Pathol Underwater digital camera with your antibody orders
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Order Full text via Infotrieve
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McGuire, E. J.
Right arrow Articles by de la Iglesia, F. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McGuire, E. J.
Right arrow Articles by de la Iglesia, F. A.

American Journal of Pathology, Vol 139, 217-229, Copyright © 1991 by American Society for Investigative Pathology

REGULAR ARTICLES

Peroxisome induction potential and lipid-regulating activity in rats. Quantitative microscopy and chemical structure-activity relationships

EJ McGuire, JA Lucas, RH Gray and FA de la Iglesia
Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105.

Structurally diverse lipid-regulating agents induce hepatomegaly, hepatic peroxisome proliferation, and hepatocarcinoma in rats by mechanisms not fully understood. Nevertheless the initial hepatic response is a prompt, florid proliferation of peroxisomes. In investigations reported here, changes in the rat hepatic peroxisome compartment were measured by quantitative microscopy to determine chemical structure requirements that relate to peroxisome proliferation and lipid regulation. Aryloxyalkanoic acids plus amide analogs, and thio, benzimidazole, phenylpiperazine, and oxazole derivatives induced peroxisome proliferation and generally decreased plasma triglyceride and total cholesterol levels. These compounds contain an acidic function or are readily metabolized to a chemical with an acidic function. Substitution of the acidic function with an adamantyloxy eliminated peroxisome proliferation and induced contrasting effects on lipid profile, increasing triglycerides and decreasing total cholesterol. A previously unreported, direct correlation emerged between peroxisome proliferation and plasma high-density lipoprotein- cholesterol levels. These effects could not be elicited separately, negating identification of functional groups that could be associated with either activity. Chemical structure and resulting peroxisome proliferation with changes in plasma lipoproteins are therefore closely interrelated in rats.




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1991 by the American Society for Investigative Pathology.