Efficacy of topical versus oral 5-aminosalicylate for treatment of 2,4,6-trinitrobenzene sulfonic acid-induced ulcerative colitis in rats

Abstract

5-aminosalicylic acid (5-ASA) is drug of choice for the treatment of ulcerative colitis (UC). In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC. A total of 60 rats were divided into sham operation group (receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube), model group, topical 5-ASA group, oral Etiasa group (a release agent of mesalazine used as positive control) and oral 5-ASA group (n=12 each). Different treatments were administered 1 day after UC induction. The normal saline (2 mL) was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group (7.5 g/L, twice per day, 100 mg/kg), and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa (7.5 g/L, twice per day, 100 mg/kg) and 5-ASA (7.5 g/L, twice per day, 100 mg/kg), respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography (HPLC). The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.

Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse

“…For certain applications, such as rectal protection against sexually transmitted diseases with microbicides or treatment of UC, colorectal drug delivery may be preferable [18, 61-63]. Our work indicates that, when administered locally to the colorectum via enema, MPP of all sizes tested provided improved distribution over the epithelial surface compared to MAP.…”

“…It is widely agreed that enhanced drug delivery from the chyme to the entire (highly-folded) GI tract epithelium, including the highly absorptive jejunum, where fluid absorption greatly speeds nutrient uptake, is desired for maximum absorption into the systemic circulation [8, 11-14]. Furthermore, for treating diseases of the colorectum, such as ulcerative colitis (UC), and for preventing rectal transmission of sexually transmitted infections (STI), rectal, rather than oral administration, may be more effective [15-18]. …”

Targeting IL‐10, ZO‐1 gene expression and IL‐6/STAT‐3 trans‐signaling by a combination of atorvastatin and mesalazine to enhance anti‐inflammatory effects and attenuates progression of oxazolone‐induced colitis

“…To ensure even distribution of oxazolone solution through the colon, the animals were kept in a vertical position for 45 s after intra‐rectal administration . Rats were randomly allocated into six equal groups (10 rats each) as follows: oxazolone group; untreated oxazolone group receiving no drugs, esalazine group (EL‐Pharaonia pharmaceutical company, Egypt); oxazolone group treated with mesalazine (100 mg/kg/day; dissolved in normal saline orally for 21 days) [18], atorvastatin group (Amoun Pharmaceutical company, Egypt); oxazolone group treated with atorvastatin (20 mg/kg/day; dissolved in normal saline administered orally for 21 days) [19,20] and combination group; oxazolone group treated with a combination of mesalazine and atorvastatin with the same dosage regimen. Along with these groups, the normal control and control saline groups received vehicle of intra‐rectal 50% ethanol in the 5th & 7th days followed by administration of 0.9 % saline solution orally daily for 21 days.…”

Manipulating Microbiota in Inflammatory Bowel Disease Treatment: Clinical and Natural Product Interventions Explored

“…Both oral and rectal administration of 5-ASA can alleviate symptoms, such as abdominal pain, rectal spasms, and urinary urgency in patients with inflammatory bowel disease (IBD) [ 77 ]. Furthermore, enema use of 5-ASA has a better inhibitory effect on inflammatory infiltration of intestinal epithelium [ 78 ]. Interestingly, 5-ASA did not alleviate the symptoms of dextran sulfate sodium (DSS) -induced colitis in mice with antibiotic-depleted intestinal flora, suggesting that the efficacy of 5-ASA is dependent on the intestinal flora [ 79 ] ( Table 1 ).…”