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Non‐steroidal anti‐inflammatory drugs with different cyclooxygenase inhibitory profiles that prevent aberrant crypt foci formation but vary in acute gastrotoxicity in a rat model 1
Author(s) -
Brown Wendy A,
Skinner Stewart A,
MalcontentiWilson Caterina,
Misajon Aileen,
Dejong Tanya,
Vogiagis Daphne,
O’Brien Paul E
Publication year - 2000
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2000.02370.x
Subject(s) - meloxicam , sulindac , medicine , etodolac , cyclooxygenase , celecoxib , pharmacology , aberrant crypt foci , valdecoxib , colorectal cancer , cox 2 inhibitor , rofecoxib , cancer , enzyme , colonic disease , chemistry , biochemistry , nonsteroidal
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.