Differential modulation of PPARα and γ target gene expression in the liver and kidney of rats treated with aspirin

Marco Fidaleo, Emanuele Berardi, Claudia Sartori

Research output: Contribution to journalArticlepeer-review

Abstract

Aspirin modified peroxisomal enzymatic activities both in the liver and renal cortex of rats, producing typical effects of peroxisomal proliferators (PPs). Although similar increments in β-oxidation system and catalase activities were observed in both organs, induction of mRNA-Cyp4a10 and mRNA-FAT/CD36, target genes for peroxisome proliferator-activated receptors α (PPARα) and γ (PPARγ), respectively, was only present in the liver. There was no effect on liver mRNA-PPARα, while mRNA-PPARγ was down-regulated, probably as a result of enzymatic inhibition of cyclooxygenases (COXs) by aspirin which has been shown to decrease the levels of PGJ2 and its metabolites, known as strong endogenous ligands for PPARγ. Typical PP alterations in cell replication and apoptosis were not found during aspirin treatment or after withdrawal, suggesting that peroxisome proliferation occurs without inducing cell cycle alterations. Probably, the synergic action of both PPARα and PPARγ receptors might reduce the impact on cell proliferation and apoptosis.

Original languageEnglish
Pages (from-to)391-397
Number of pages7
JournalExperimental and Toxicologic Pathology
Volume59
Issue number6
DOIs
Publication statusPublished - Apr 3 2008

Keywords

  • Apoptosis
  • Aspirin
  • Cell proliferation
  • Cyclooxygenase
  • Peroxisome proliferator-activated receptors
  • Peroxisome proliferators

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Pathology and Forensic Medicine
  • Toxicology

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