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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 71 (1993), S. 286-289 
    ISSN: 1432-1440
    Keywords: (Na+ + K+)-ATPase ; Inflammatory bowel disease ; Diarrhea ; 5-Aminosalicyclic acid ; Olsalazine ; Mesalazine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Olsalazine (azodisalicylate) and mesalazine (5-aminosalicylic acid) have recently been developed as new treatment modalities for inflammatory bowel disease to avoid sulfasalazine-related side effects. However, there are reports regarding new and hitherto unexpected side effects in some patients receiving olsalazine or mesalazine, such as watery diarrhea. Since sodium pump activities play an important role in the pathogenesis of water and electrolyte disturbances, we investigated the influence of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase and its specific [3H]-ouabain binding. We found a concentration-dependent inhibition of ileal and colonic (Na+ + K+)-ATPase by olsalazine with an IC50 of 4.1 mM and 4.8 mM, respectively. Mesalazine inhibited this enzyme in the ileum with an IC50 of 4.5 mM and in the sigmoid colon with an IC50 3.5 mM. In addition, [3H]-ouabain binding was inhibited by mesalazine with an IC50 of 3.6 mM. The maximal inhibition, however, did not exceed 80% under any conditions (up to 10 mM drug concentration). Olsalazine and mesalazine induce inhibition of the ileal and colonic sodium pump activities that may (in addition to other possible mechanisms) mediate impaired water and electrolyte absorption. This is possibly of clinical relevance in patients with severely damaged mucosa. In patients with milder forms of mucosal inflammation, this inhibition most likely is of minor importance because of the great capacitiy of the (Na+ + K+)-ATPase and the incomplete inhibition leaving at least 20% of the enzyme activity intact.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-2568
    Keywords: BASE HYDROXYLATION ; BILE ACIDS ; AMINOSALICYLIC ACID ; N-ACETYL-AMINOSALICYLIC ; SALICYLATE ; CHEMOPREVENTION ; COLON CANCER ; INFLAMMATORY BOWEL DISEASE ; COLONIC DNA MODEL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bile acids are believed to be involved in theformation of colonic cancer, and 5-aminosalicylic acidand other salicylates may have a protective role. Theprecise mechanisms of both actions are not known, but modifications (stimulation or inhibition)of basal or oxygen-radical induced DNA basehydroxylation as potential early events in tumorformation by these compounds may be involved in suchactions. We, therefore, investigated whether: (1) bile acidsin concentrations as they occur systemically orintraluminally are able to enhance basal orOH-radical-stimulated base hydroxylation in DNA fromcalf thymus; (2) 5-aminosalicylic acid, its main intestinalmetabolite N -acetyl-aminosalicylic acid and salicylate,the main aspirin metabolite, are able to inhibit thishydroxylation; and (3) DNA from calf thymus can be used as a model by comparing its basecomposition and hydroxylation with DNA from normal humancolonic mucosa. We found an enhancement of theOH-radical-induced DNA hydroxylation especially 8-OH adenine with 214.0%. On the other hand 5-ASA,N -acetylASA, and salicylate showed aconcentration-dependent inhibition of OH-stimulatedhydroxylation with IC50 between 0.04 ±0.01 mM (X ± SD) and 1.3 ± 0.1 mM. No effects were observed onbasal hydroxylation. Electron spin resonancespectroscopy studies showed reduction of thecorresponding base signals pointing to a scavengermechanism. In DNA isolated from normal human colonic mucosa (N =7) a similar base distribution was found as in calfthymus; hydroxylation was 1.0% in both systems. From ourresults we conclude that DNA from calf thymus may serve as a model for human colonic mucosalDNA and that one of the carcinogenic actions of bileacids may be enhancement of oxygen-radical-induced DNAbase hydroxylation, especially 8-OH adenine. The absence of effects under unstimulatedconditions supports their role as cocarcinogens. Theconcentration-dependent inhibition of OH-stimulated DNAhydroxylation by 5-ASA, salicylate, and N-acetyl-ASA may be a possible mechanism ofchemoprevention.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-2568
    Keywords: inflammatory bowel disease ; (Na+ + K+)-ATPase ; 5′-nucleotidase ; mucosal inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In inflammatory bowel disease (IBD), mucosal damage and loss of colonic function are regarded as major consequences of inflammation. Decreased colonic (Na+ + K+)-ATPase activities with diminished reabsorption of sodium and water have been found in active stages of ulcerative colitis. In this study, we report an inverse relationship between colonic (Na+ + K+)-ATPase activity and the degree of mucosal inflammation in 19 patients with IBD of mild to moderate disease activity. Various macroscopic and histologic types of mucosal lesions were differently associated with the (Na+ + K+)-ATPase activities. 5′-nucleotidase activity was not associated with the degree of mucosal inflammation or the kind of macroscopic or histologic lesions. Our findings support the view that, in contrast to 5′-nucleotidase, (Na+ + K+)-ATPase activity may better reflect the severity of mucosal damage and the degree of inflammation in IBD.
    Type of Medium: Electronic Resource
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