Autor: |
Brown, Wendy A, Skinner, Stewart A, Malcontenti-Wilson, Caterina, Misajon, Aileen, Dejong, Tanya, Vogiagis, Daphne, O’Brien, Paul E |
Předmět: |
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Zdroj: |
Journal of Gastroenterology & Hepatology; Dec2000, Vol. 15 Issue 12, p1386-1392, 7p, 2 Charts, 2 Graphs |
Abstrakt: |
Abstract Background Standard non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal cancer; however, their use as preventive agents is limited by their inherent toxicity. Drugs that selectively inhibit cyclooxygenase-2 (COX-2) may be useful in this setting as they are supposedly less toxic. No study has directly compared the ability of standard NSAIDs and selective COX-2 inhibitors to inhibit colorectal cancer at clinically relevant doses. Methods Aberrant crypt foci (ACF) were induced in Sprague–Dawley rats by using 1,2-dimethylhydrazine (DMH). Test agents or vehicle were then administered for 3 weeks, twice daily through orogastric gavage. At the end of this period, the number and multiplicity of ACF were determined. The agents tested at equivalent anti-inflammatory doses were: sulindac and indomethacin (standard NSAIDs), meloxicam (selective COX-2 inhibitor), celecoxib (specific COX-2 inhibitor) and sulindac sulfone (no known COX activity). Acute gastrotoxicity of NSAID in rats was compared by using quantitative histology. Results All test agents reduced the number of ACF. There was a 42% reduction with indomethacin, 46% with sulindac, 46% with meloxicam, 22% with celecoxib and 36% with sulindac sulfone. Only the COX-2 inhibitors caused no significant gastrotoxicity in rats. Conclusions Cyclooxygenase-2 inhibitors are potentially ideal chemopreventive agents as they inhibit ACF and are not gastrotoxic. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
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