title: The cyclopentenone prostaglandin 15-deoxy-delta(12,14)- PGJ2 attenuates the development of colon injury caused by dinitrobenzene sulphonic acid in the rat.
abstract: 1. Inflammatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leukocyte infiltration, and increased expression of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) in the colon. Recent evidence also suggests that the cyclopentenone prostaglandin (PG) 15-deoxy-delta(12,14)-PGJ(2) (15d- PGJ(2)) functions as an early anti-inflammatory signal. 2. The aim of the present paper is to investigate the effects of 15d-PGJ(2) in rats subjected to experimental colitis. 3. Colitis was induced in rats by intra-colonic instillation of dinitrobenzene sulphonic acid (DNBS). 15d-PGJ(2) was administered daily as intraperitoneal injection (20 or 40 microg kg(-1)). On day 4, animals were sacrificed and tissues were taken for histological and biochemical analysis. 4. 15d-PGJ(2) significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. 15d-PGJ(2) also caused a substantial reduction of (i) the degree of colonic injury, (ii) the rise in myeloperoxidase (MPO) activity (mucosa), (iii) the increase in the tissue levels of malondialdehyde (MDA) and (iv) of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). 5. Furthermore, 15d-PGJ(2) reduced the increase in immunohistochemical staining for (i) inducible nitric oxide synthase (iNOS), (ii) nitrotyrosine and (iii) poly (ADP-ribose) polymerase (PARP), as well as (iv) the increased expression of ICAM-1 caused by DNBS in the colon. 6. Electrophoresis mobility shift assay (EMSA) of inflamed colon revealed that 15d- PGJ(2) also caused a substantial reduction of the activation of nuclear factor-kappaB (NF-kappaB). Furthermore, 15d-PGJ(2) stimulates the activation of heat shock protein 72 (hsp72) in the inflamed colon, as assessed by Western blot analysis. 7. In conclusion, 15d-PGJ(2) reduces the development of experimental colitis.
authors.affiliation: Institute of Pharmacology, University of Messina, Italy. salvator@unime.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Angela
authors.initials: A
authors.lastname: Ianaro
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Wayman
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Barbara
authors.initials: B
authors.lastname: Pisano
authors.forename: Laura
authors.initials: L
authors.lastname: Dugo
authors.forename: Ivana
authors.initials: I
authors.lastname: Serraino
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Prabal K
authors.initials: PK
authors.lastname: Chatterjee
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Rosa
authors.forename: Achille P
authors.initials: AP
authors.lastname: Caputi
authors.forename: Christoph
authors.initials: C
authors.lastname: Thiemermann
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000633:toxicity*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D001557:Benzenesulfonates; C007488:dinitrobenzenesulfonic acid; D015230:Prostaglandin D2