Abstract
Ulcerative colitis (UC) is a chronic, recurrent bowel disorder accompanied by inflammation and increased oxidative stress within the bowel. This study was designed to investigate the therapeutic effectiveness of a-lipoic acid (ALA) and omega-3 polyunsaturated fatty acids (OM3) in a rat model of colitis induced by acetic acid (AA), and to determine whether NF-kappa beta signaling and its downstream inflammatory pathways are involved in the underlying mechanisms. Adult Wistar male rats (n = 8) were randomized into five equal groups: (1) Control (saline-treated), (2) AA model, (3) AA/ALA (100 mg/kg), (4) AA/OM3 (200 mg/kg), and (5) AA/ALA/OM3. Animals in groups 2 through 5 were treated using intra-gastric administration of either ALA or OM3 or a combination of ALA and OM3 for seven days. The combined treatment of ALA and OM3 dramatically attenuated AA-induced colitis, reversed bodyweight loss, and improved histopathological changes. In addition, TBARS, the biomarker of lipid peroxidation, was decreased, while the GSH level (along with CAT and SOD activities) were increased. In addition, combined ALA/OM3 treatment attenuated the histopathological inflammatory hallmarks and reduced the colonic expression of NF-kappa beta p65 signaling and the levels of pro-inflammatory cytokines (IL-1 beta, IL-6, TNF-alpha, and MPO). The combined oral ALA/OM3 treatment had a greater protective effect against AA-induced UC than treatments using either substance individually. This protective effect is probably mediated by reducing oxidative stress and upregulating antioxidant defenses, in addition to inhibiting NF-kappa beta signaling and its downstream inflammatory cascade. The combined treatment is an encouraging new strategy for the treatment of UC.