The cyclopentenone prostaglandin 15-deoxy Delta(12,14)-prostaglandin J(2) attenuates the development of zymosan-induced shock

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-&UDelta;(12,14)-PGJ(2) (15d-PGJ(2)), 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-PGJ(2) (30 μ g/kg, suspended in 10% DMSO) 1 h before and 6 h after zymosan administration; group 3, 15d-PGJ(2) (30 μ g/kg, suspended in 10% DMSO; group 4, vehicle for PGJ(2) (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-PGJ(2) 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-PGJ(2) also reduced the appearance of nitrotyrosine in the inflamed intestinal tissues. Histological examination revealed a significant reduction in zymosan-induced intestinal damage in 15d-PGJ(2) treated mice. Conclusions: Our findings demonstrate that 15d-PGJ(2) exerts potent anti-inflammatory effects on zymosan-induced shock.