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The cyclopentenone prostaglandin 15-deoxyΔ12,14-prostaglandin J2 attenuates the development of zymosan-induced shock

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Abstract

Objective

Multiple-organ failure (MOF) is defined as the progressive deterioration in function which occurs in several organs or systems in patients with septic shock, multiple trauma, severe burns, or pancreatitis. This study investigated the effect of 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), a PPAR-γ ligand, in a model of zymosan-induced nonseptic shock in mice.

Materials and methods

Mice were randomly assigned to one of four groups (n=10 each) and treated i.p. as follows: group 1, zymosan (500 mg/kg suspended in saline solution) and vehicle (10% DMSO); group 2, zymosan (500 mg/kg suspended in saline solution) plus 15d-PGJ2 (30 µg/kg, suspended in 10% DMSO) 1 h before and 6 h after zymosan administration; group 3, 15d-PGJ2 (30 µg/kg, suspended in 10% DMSO; group 4, vehicle for PGJ2 (10% DMSO) always 1 h before and 6 h after saline administration. After 18 h mice were killed and tissues and biological fluids used for biochemical, immunohistochemical, and histological analysis.

Measurements and results

15d-PGJ2 inhibited the inflammatory response and significantly reduced peritoneal mononuclear cell infiltration and histological injury in mice. A significant protection was demonstrated in kidney, liver, and pancreas injury by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubin, and alkaline phosphatase levels. 15d-PGJ2 also reduced the appearance of nitrotyrosine in the inflamed intestinal tissues. Histological examination revealed a significant reduction in zymosan-induced intestinal damage in 15d-PGJ2 treated mice.

Conclusions

Our findings demonstrate that 15d-PGJ2 exerts potent anti-inflammatory effects on zymosan-induced shock.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Salerno, Fisciano-Salerno, Italy

    Stefania Marzocco, Aldo Pinto & Giuseppina Autore

  2. Institute of Pharmacology, School of Medicine, , University of Messina, Torre Biologica-Policlinico Universitario, Via C. Valeria, Gazzi, 98100, Messina, Italy

    Rosanna Di Paola, Emanuela Mazzon, Tiziana Genovese & Salvatore Cuzzocrea

  3. Institute of Pharmacology, University of Messina, Messina, Italy

    Domenico Britti

Authors
  1. Stefania Marzocco
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  2. Rosanna Di Paola
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Correspondence to Salvatore Cuzzocrea.

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Marzocco, S., Di Paola, R., Mazzon, E. et al. The cyclopentenone prostaglandin 15-deoxyΔ12,14-prostaglandin J2 attenuates the development of zymosan-induced shock. Intensive Care Med 31, 693–700 (2005). https://doi.org/10.1007/s00134-005-2596-2

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