P068. Hyperbaric oxygen reduces hypoxia-inducible factor-1 alpha expression in experimental acute distal colitis
R.S. Parra1, E. Uchoa Carreira2, A.H.P. Lopes2, T.M. Cunha2, S.B. Garcia3, F. Queiroz Cunha2, J. Joaquim Ribeiro da Rocha1, O. Féres1, 1University of São Paulo, Surgery and Anatomy, Ribeirao Preto SP, Brazil, 2University of São Paulo, Pharmacology, Ribeirao Preto SP, Brazil, 3University of São Paulo, Pathology, Ribeirao Preto SP, Brazil
This study investigated the therapeutic effects of hyperbaric oxygen (HBO) in experimental acute distal colitis focusing on its effect on cytokines and HIF-1alpha.
Twenty-eight Wistar rats were divided into four groups (each group had 7 rats): I (Saline); II (Saline/HBO); III (TNBS); and IV (TNBS+HBO). Colitis was induced with a rectal infusion of 150 mg/kg of trinitrobenzenesulfonic acid-ethanol (TNBS) under anesthesia with Ketamine (50 mg/kg) and Xylazine (10 mg/kg). Control animals received only rectal saline. After induction, the colitis animals were subjected to two sessions of HBO and were then euthanized. The distal intestine was resected for macroscopic analysis, myeloperoxidase activity (MPO) measurements, Western-blot analyses of nitric oxide synthase activity (iNOS) and Cicloxygenase-2 (COX-2) and immunohistochemical analysis of HIF-1alpha and COX-2. Cytokines levels (IL-1beta, CINC-1, IL-10 and TNF-alpha) in the distal intestine were measured using an enzyme-linked immunosorbent assay (ELISA).
HBO therapy attenuated the severity of acute distal colitis, with reduced macroscopic damage score and reduced cytokine expression. HBO therapy inhibited the acute distal colitis-induced up-regulation of HIF-1alpha and its downstream iNOS and myeloperoxidase activity, as well as producing diminished COX-2 levels.
The results indicate that HBO therapy attenuates the severity of acute distal colitis through the down-regulation of the expression of HIF-1alpha and pro-inflammatory cytokines.