The cyclopentenone prostaglandin 15‐deoxy‐Δ^12,14‐ PGJ₂ attenuates the development of colon injury caused by dinitrobenzene sulphonic acid in the rat

Abstract

1 In¯ammatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leukocyte in®ltration, 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-D 12,14 -PGJ 2 (15d-PGJ 2 ) functions as an early anti-in¯ammatory signal. 2 The aim of the present paper is to investigate the e ects 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 mg kg 71 ). On day 4, animals were sacri®ced and tissues were taken for histological and biochemical analysis. 4 15d-PGJ 2 signi®cantly 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-in¯ammatory cytokines tumour necrosis factoralpha (TNF-a) and interleukin-1b (IL-1b). 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 in¯amed colon revealed that 15d-PGJ 2 also caused a substantial reduction of the activation of nuclear factor-kappaB (NF-kB). Furthermore, 15d-PGJ 2 stimulates the activation of heat shock protein 72 (hsp72) in the in¯amed colon, as assessed by Western blot analysis. 7 In conclusion, 15d-PGJ 2 reduces the development of experimental colitis.

Atorvastatin protected from paraquat-induced cytotoxicity in alveolar macrophages via down-regulation of TLR-4

“…The rate of change in the optical density was measured at 650 nm spectrophotometerically. One unit of the MPO activity was defined as that degrading 1 mol of H 2 O 2 per minute at 37 • C and was expressed as units per one million cells (Cuzzocrea et al, 2003).…”

Comparative Protective Effect of Hawthorn Berry Hydroalcoholic Extract, Atorvastatin, and Mesalamine on Experimentally Induced Colitis in Rats

“…21 In brief, the specimens were homogenized in a 10 mM potassium phosphate buffer (pH 7.0), containing 0.5% hexadecyl trimethyl ammonium bromide and centrifuged at 20,000 g for 30 min at 4°C. A solution of 1.6 mM tetramethylbenzidine and 0.1 mM hydrogen peroxide (H 2 O 2 ) was added and reacted with an aliquot of the supernatant.…”

Benefit of nicorandil using an immunologic murine model of experimental colitis

“…The severity of colitis was assessed using the colon macroscopic scoring as described previously [34] ( Table 1). …”

“…The scoring was performed by an observer blind to the identity of each treated group, as described previously [34] ( Table 2).…”