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.