Absence of peroxisome proliferators-activated receptors (PPAR) α enhanced the multiple organ failure induced by zymosan

Rosanna Di Paola, Emanuela Esposito, Emanuela Mazzon, Tiziana Genovese, Carmelo Muià, Concetta Crisafulli, Giuseppe Malleo, Edoardo Sessa, Rosaria Meli, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

The peroxisome proliferator-activated receptor (PPAR) α is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. The aim of the present study is to evaluate the role of PPAR-α receptor on the development of multiple-organ dysfunction syndrome (MODS) induced by zymosan. MODS was induced by peritoneal injection of zymosan (dose, 500 mg/kg i.p. as a suspension in saline) in PPAR-α wild-type (PPAR-αWT) and PPAR-α knockout (PPAR-αKO) mice, was assessed 18 h after the administration of zymosan, and was monitored for 12 days (for loss of body weight and mortality). A severe inflammatory process, induced by zymosan administration in wild-type mice, coincided with the damage of liver, kidney, pancreas, and small intestine. Myeloperoxidase activity, indicative of neutrophil infiltration, and lipid peroxidation were significantly increased in zymosan-treated wild-type mice. Zymosan in the wild-type mice also induced a significant increase in the plasma levels of nitrite/nitrate. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine and Fas ligand in the intestine of zymosan-treated wild-type mice. In contrast, the degree of (1) peritoneal inflammation and tissue injury, (2) nitrotyrosine formation and Fas ligand expression, and (3) neutrophil infiltration were markedly enhanced in intestinal tissue obtained from zymosan-treated PPAR-αKO mice. Zymosan-treated PPAR-αKO mice also showed a significantly increased mortality. Taken together, the present study clearly demonstrates that PPAR-α pathway modulates the degree of MODS associated with zymosan-induced nonseptic shock.

Original languageEnglish
Pages (from-to)477-484
Number of pages8
JournalShock
Volume26
Issue number5
DOIs
Publication statusPublished - Nov 2006

Keywords

  • Inflammation
  • Multiple-organ failure
  • PPAR-α
  • Shock
  • Systemic inflammation
  • Zymosan

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Fingerprint Dive into the research topics of 'Absence of peroxisome proliferators-activated receptors (PPAR) α enhanced the multiple organ failure induced by zymosan'. Together they form a unique fingerprint.

  • Cite this

    Di Paola, R., Esposito, E., Mazzon, E., Genovese, T., Muià, C., Crisafulli, C., Malleo, G., Sessa, E., Meli, R., & Cuzzocrea, S. (2006). Absence of peroxisome proliferators-activated receptors (PPAR) α enhanced the multiple organ failure induced by zymosan. Shock, 26(5), 477-484. https://doi.org/10.1097/01.shk.0000230299.78515.2c