The cyclopentenone prostaglandin 15-deoxy-Delta12,14- PGJ2 attenuates the development of colon injury caused by dinitrobenzene sulphonic acid in the rat
Cuzzocrea, S., Ianaro, A., Wayman, N.S., Mazzon, E., Pisano, B., Dugo, L., Serraino, I., Di Paola, R., Chatterjee, P.K., Di Rosa, M., Caputi, A.P. and Thiemermann, C. (2003) The cyclopentenone prostaglandin 15-deoxy-Delta12,14- PGJ2 attenuates the development of colon injury caused by dinitrobenzene sulphonic acid in the rat British Journal of Pharmacology, 138 (4). pp. 678-688. ISSN 0007-1188
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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-Delta12,14-PGJ2 (15d- PGJ2) functions as an early anti-inflammatory signal. 2. The aim of the present paper is to investigate the effects of 15d-PGJ2 in rats subjected to experimental colitis. 3. Colitis was induced in rats by intra-colonic instillation of dinitrobenzene sulphonic acid (DNBS). 15d-PGJ2 was administered daily as intraperitoneal injection (20 or 40 mug kg-1). On day 4, animals were sacrificed and tissues were taken for histological and biochemical analysis. 4. 15d-PGJ2 significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. 15d-PGJ2 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-PGJ2 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- PGJ2 also caused a substantial reduction of the activation of nuclear factor-kappaB (NF-kappaB). Furthermore, 15d-PGJ2 stimulates the activation of heat shock protein 72 (hsp72) in the inflamed colon, as assessed by Western blot analysis. 7. In conclusion, 15d-PGJ2 reduces the development of experimental colitis.
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