Effect Of 5-aminosalicylic Acid Research Articles

Effect of 5-amino salicylic acid on oxazolone induced ulcerative colitis in adult zebrafish model

Effect of 5-amino salicylic acid on oxazolone induced ulcerative colitis in adult zebrafish model

Effect of 5-aminosalicylic acid on radiation-induced micronuclei in mouse bone marrow

5-Aminosalicylic acid (5ASA), a prescribed drug for ulcerative colitis, is a potent scavenger of oxygen-derived free radicals. The present study was undertaken to ascertain its ability to protect against radiation-induced damage. The drug dose-dependent effect, optimum time of drug administration and radiation dose-dependent effect (0–4 Gy) on in vivo radiation protection against micronuclei induction in polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were studied in the bone marrow of mice. Intraperitoneal injection of 10–125 mg/kg of the drug 30 min before whole body irradiation with 3 Gy produced a significant reduction in the frequency of micronucleated erythrocytes at 24 h after exposure. The optimum dose for protection without drug toxicity was 25 mg/kg body weight. Injection of 25 mg/kg of the drug 60 or 30 min before or within 15 min after 3 Gy whole body γ-irradiation resulted in a significant decrease in the radiation-induced PCE and NCE with micronuclei (MPCE and MNCE) and an increase in the ratio of PCE to NCE (P/N), at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. Therefore, to study the radiation dose–response, mice were pre-treated with 25 mg/kg of 5ASA 30 min before 1–4 Gy of γ-irradiation. Radiation increased the MN frequency linearly ( r 2=0.99) with dose. Pre-treatment with 5ASA significantly reduced the MN counts to 40–50% of the radiation (RT) alone values, giving a dose modification factor (DMF) of 2.02 (MPCE) and 2.53 (MNCE). Irradiation resulted in a dose-dependent decline in the P/N ratio at all the doses of radiation studied. 5ASA produced a significant increase in the P/N ratio from that of irradiated controls, at all doses of radiations tested. These results show that 5ASA protect mice against radiation-induced MN formation and mitotic arrest.

Medical therapies for ulcerative colitis and Crohn's disease.

This review focuses on data reported in the last year on medical treatment of Crohn's disease and ulcerative colitis. In Crohn's disease, a broad range of cytokine-based therapies are currently being tested. Although all are very exciting, the anti-tumor-necrosis-factor (TNF) approach remains the most effective, with infliximab (a chimeric monoclonal antibody directed against TNF) being the most active agent. With repeated infusions every 8 weeks, remission is induced and can be maintained even in refractory patients with no major apparent side effects. Thalidomide, an oral agent with anti-TNF effects, shows promise in non-controlled experience. Important new data on azathioprine/6-mercaptopurine (6-MP) and its metabolites are also helpful. Methotrexate can induce remissions in 6-MP-allergic or refractory Crohn's patients and has now shown efficacy as a maintenance agent. Beneficial effects are also reported for a variety of new agents: mycophenolate mofetil, tacrolimus (FK506), growth hormone, and granulocyte colony-stimulating factor (G-CSF). Important observations in ulcerative colitis (UC) over the past year include evidence of a protective effect of 5-aminosalicylic acid (5-ASA) with respect to colorectal cancer, negative results from a study for heparin monotherapy, and results from a comparison of mycophenolate mofetil versus azathioprine as maintenance therapy. Epidemiologically, the negative association between appendectomy and UC was corroborated in a meta-analysis, suggesting an immunologic role for this organ. Finally, in chronic pouchitis, probiotic therapy was found to maintain remissions very significantly.

The effect of 5-aminosalicylic acid on inducible nitric oxide synthase expression and activity in the colonic epithelial cell line HT-29

The effect of 5-aminosalicylic acid on inducible nitric oxide synthase expression and activity in the colonic epithelial cell line HT-29

Effect of 5-aminosalicylic acid and 4-aminosalicylic acid on precontracted rat aortic strips and on NO-mediated inhibition of platelet aggregation

We have examined the interactions of 5-aminosalicylic acid (5-ASA) and 4-aminosalicylic acid (4-ASA) with nitric oxide (NO) on rat aorta and human platelets. Phennylephrine-precontracted rat aortic strips with intact endothelium were further contracted by 5-ASA (50–200 μmol/1) and 4-ASA (1–20 mmol/1) in a concentration-dependent manner. Removal of endothelium, inhibition of guanylate cyclase by methylene blue, inhibition of NO biosynthesis byNG-nitro-l-arginine as well as inactivation of NO by oxyhemoglobin abolished the effects of 5-ASA and 4-ASA. The antiaggregatory effects of 3-morpholinosydnonimine (SIN-1) and rat peritoneal neutrophils (RPN) were diminished in a concentration-dependent manner by 5-ASA (50–250 μmol/l), but not by 4-ASA (up to 20 mmol/l). In the presence of superoxide dismutase (SOD), 5-ASA did not antagonize NO-mediated effects on platelets. 5-ASA up to 100 μmol/l did not affect NO synthase from rat brain, while a concentration of 1 mM caused 21% inhibition. Since NO might act as a cytotoxic mediator, our results suggest that inactivation of NO by 5-ASA and higher concentrations of 4-ASA could contribute to the therapeutic activity of the drugs in inflammatory bowel disease (IBD).

Effect of 5-aminosalicylic acid and analogous substances on superoxide generation and intracellular free calcium in human neutrophilic granulocytes.

Activated polymorphonuclear leukocytes (PMNs), which are found in the inflammatory lesions of chronic inflammatory bowel disease, produce tissue-destructive oxygen-derived free radicals. The influence of 5-aminosalicylic acid (5-ASA), its acetylated metabolite (Ac-5-ASA), sulfasalazine (SAZ), and olsalazine (OLZ) (5-ASA dimer linked by an azo group) in pharmacologically relevant concentrations (0.1-10 mM) were tested on PMN superoxide production with either the receptor-specific agent formyl-methionyl-leucyl-phenylalanine (fMLP) or the protein kinase C activator phorbol myristate acetate (PMA). Inhibition of receptor-specific superoxide production occurred at 0.07, 0.32, and 0.63 mM (IC50 values) for 5-ASA, SAZ, and OLZ, respectively. No inhibitory effects of SAZ and OLZ were observed when PMA was applied as stimulus for PMN superoxide production. The results indicate that the signal to which PMNs respond by generating superoxide is primarily due to calcium release from intracellular stores. They further suggest that SAZ and OLZ may affect the oxygen-derived free radical production in human PMNs by unspecific cytotoxicity or by interference with the nicotinamide adenine dinucleotide phosphate, reduced (NADPH) oxidase system, whereas 5-ASA itself is a free radical scavenger.

Involvement of oxygen-derived free radicals in the pathogenesis of chronic inflammatory bowel disease

Ulcerative colitis and Crohn's disease are chronic inflammatory bowel diseases. The most widely prescribed drug for treatment of these diseases, sulfasalazine, has been shown to inhibit the activity of free radicals, as the active moiety of sulfasalazine, 5-aminosalicylic acid, is a radical scavenger. This effect of 5-aminosalicylic acid may be of clinical relevance, as a recent study has shown that 5-aminosalicylic acid reacts with oxygen-derived free radicals formed in the intestine in this disease. Reaction with free radicals does not, however, occur in patients with rheumatoid arthritis treated with the same agent. Furthermore, a significant correlation exists between the activity in the intestine of free radicals, as measured by the rate of lipid peroxidation, and the disease activity.

Effect of 5-aminosalicylic acid on ferrous sulfate-mediated damage to deoxyribose

Because some salicylate derivatives are known to chelate iron and because iron is thought to play a role in inflammatory tissue injury, we assessed the possibility that 5-ASA may behave as an iron chelator and thus may protect deoxyribose from iron-catalyzed . OH-mediated damage

Effect of 5-aminosalicylic acid (5-ASA) and other salicylates on short-chain fat metabolism in the colonic mucosa: Pharmacological implications for ulcerative colitis

5-Aminosalicylic acid (5-ASA) suppressed nitrite-stimulated oxidation of the fatty acid n-butyrate in a dose-dependent manner in isolated human and rat colonie epithelial cells. 4-ASA had one-sixth of the capacity of 5-ASA and sulphapyridine (SP) little of the capacity of 5-ASA to suppress fatty acid oxidation in human colonie epithelial cells. Sulphasalazine (SASP), azodisalicylic acid (ADS), acetyl-5-ASA and acetyl salicylic acid (ASA) did not suppress fatty acid oxidation in rat colonocytes. The suppression index of fatty acid oxidation (SIFO) of respective salicylic acids correlated with the reported clinical effectiveness of each drug against ulcerative colitis (UC). The capacity of 5-ASA to affect nitrite-stimulated oxidation of fat in the colonie mucosa suggests that nitrite ions and control of fatty acid oxidation play a central role in the development and therapy of active UC.