title: Protection against 2,4,6-trinitrobenzenesulphonic acid-induced colonic inflammation in mice by the marine products bolinaquinone and petrosaspongiolide M.
abstract: Proinflammatory mediators, namely eicosanoids, reactive oxygen and nitrogen species and cytokines, are clearly involved in the pathogenesis of intestinal bowel disease. bolinaquinone (BQ) and petrosaspongiolide M (PT), two marine products with potent anti-inflammatory action, have been shown to control the production of mediators in acute and chronic inflammatory processes. Hence, we have tested here the hypothesis that BQ and PT could ameliorate inflammation and oxidative stress parameters in 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis in Balb/c mice. BQ and PT were given orally in doses of 10 or 20mg/kg/day. Treatment of the animals with BQ or PT at the highest dose significantly protected against TNBS-induced inflammation, as assessed by a reduced colonic weight/length ratio and histological scoring. Neutrophilic infiltration, interleukin (IL)-1beta and prostaglandin E(2) (PGE(2)) levels, as well as cyclooxygenase-2 (COX-2) protein expression were inhibited by both compounds. Colonic nitrite and nitrate levels and protein expression of inducible nitric oxide synthase (iNOS) were also lower in the treated groups in comparison to the TNBS control. BQ and PT reduced nitrotyrosine immunodetection and colonic superoxide anion production. Neither compound inhibited the expression of the protective protein heme oxygenase-1 (HO-1), although they reduced the extension of apoptosis. Our study also indicated that PT could interfere with the translocation of p65 into the nucleus, a key step in nuclear factor-kappaB (NF-kappaB) activation. Altogether, the results suggest that BQ and PT can have potential protective actions in intestinal inflammatory diseases.
authors.affiliation: Departamento de Farmacología, Universidad de Valencia, Facultad de Farmacia, Av. Vicent Andrés Estellés s/n, Valencia 46100, Spain.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Busserolles
authors.forename: Miguel
authors.initials: M
authors.lastname: Payá
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: D'Auria
authors.forename: Luigi
authors.initials: L
authors.lastname: Gomez-Paloma
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Alcaraz
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000032:analysis; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D047088:Dysidea / Q000737:chemistry*; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D012717:Sesquiterpenes / Q000494:pharmacology*; D050863:Synaptotagmin I; D050857:Synaptotagmins; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D002135:Calcium-Binding Proteins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012717:Sesquiterpenes; D050863:Synaptotagmin I; C500927:bolinaquinone; C118309:petrosaspongiolide m; D050857:Synaptotagmins; D009828:Oleanolic Acid; D014302:Trinitrobenzenesulfonic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases