Induction of hepatic peroxisome proliferation in nonrodent species, including primates

J. K. Reddy, N. D. Lalwani, S. A. Qureshi, M. K. Reddy, C. M. Moehle

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119 Scopus citations

Abstract

It is well established that the administration to rodents of a variety of structurally diverse chemicals possessing hypotriglyceridemic properties results in hepatomegaly, the induction of hepatic peroxisome (microbody) proliferation, and the development of hepatocellular carcinomas. Studies have led to the hypothesis that persistent proliferation of peroxisomes serves as an endogenous initiator of neoplastic transformation in liver by increasing the intracellular production of H2O2 by the peroxisomal oxidase(s). The objective of the present study was to determine whether hepatic peroxisome proliferation can be induced in cats, chickens, pigeons, and two species on monkeys (rhesus and cynomolgus). The hypolipidemic drug ciprofibrate (2-[4-2,2-dichlorocylopropyl)phenoxyl]2-methylpropionic acid) induced peroxisome proliferation in the livers of cats (dose, >40 mg/kg body weight for 4 weeks); chickens (dose >25 mg/kg body weight for 4 weeks); pigeons (300 mg/kg mg/kg body weight for 3 weeks), rhesus monkeys (50 to 200 mg/kg body weight for 7 weeks) and cynomolgus monkeys (400 mg/kg body weight for 4 weeks). In all five species examined in this study, a marked but variable increase in the activities of peroxisomal catalase, carnitine acetyltransferase, heat-labile enoyl-CoA hydratase and the fatty acid β-oxidation system was observed. These results suggest that peroxisome proliferation can be induced in the livers of several species and that it is a dose-dependent but not a species-specific phenomenon.

Original languageEnglish (US)
Pages (from-to)171-183
Number of pages13
JournalAmerican Journal of Pathology
Volume114
Issue number1
StatePublished - 1984

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Reddy, J. K., Lalwani, N. D., Qureshi, S. A., Reddy, M. K., & Moehle, C. M. (1984). Induction of hepatic peroxisome proliferation in nonrodent species, including primates. American Journal of Pathology, 114(1), 171-183.