The cyclopentenone prostaglandin 15-deoxydelta(12,14)-prostaglandin J2 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-delta(12,14)-PGJ2 (15d-PGJ2), a PPAR-gamma ligand, in a model of zymosan-induced nonseptic shock in mice.


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 microg/kg, suspended in 10% DMSO) 1 h before and 6 h after zymosan administration; group 3, 15d-PGJ2 (30 microg/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.


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.
Marzocco
Stefania
S
Department of Pharmaceutical Sciences, University of Salerno, Fisciano-Salerno, Italy.
Di Paola
Rosanna
R
Mazzon
Emanuela
E
Genovese
Tiziana
T
Britti
Domenico
D
Pinto
Aldo
A
Autore
Giuseppina
G
Cuzzocrea
Salvatore
S
D000704:Analysis of Variance; D000818:Animals; D021461:Animals, Outbred Strains; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D051379:Mice; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D047495:PPAR gamma / Q000276:immunology*; D030421:Peroxynitrous Acid / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D011897:Random Allocation; D015054:Zymosan
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D047495:PPAR gamma; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D015054:Zymosan; D015230:Prostaglandin D2