PT  - JOURNAL ARTICLE
AU  - Matteo Fornai
AU  - Luca Antonioli
AU  - Rocchina Colucci
AU  - Carolina Pellegrini
AU  - Giulio Giustarini
AU  - Lara Testai
AU  - Alma Martelli
AU  - Antuela Matarangasi
AU  - Gianfranco Natale
AU  - Vincenzo Calderone
AU  - Carmelo Scarpignato
AU  - Marco Tuccori
AU  - Corrado Blandizzi
TI  - NSAID-induced enteropathy: are the currently available selective COX-2 inhibitors all the same?
AID  - 10.1124/jpet.113.207118
DP  - 2013 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.113.207118
4099  - http://jpet.aspetjournals.org/content/early/2013/10/17/jpet.113.207118.short
4100  - http://jpet.aspetjournals.org/content/early/2013/10/17/jpet.113.207118.full
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce intestinal mucosal damage, but the underlying mechanisms remain poorly understood. The present study investigated the effects of celecoxib, etoricoxib, indomethacin and diclofenac on small bowel integrity in rats. Male rats were treated orally with test drugs for 14 days. Animals were processed for the assessment of blood hemoglobin levels, hepatic mitochondrial functions, microscopic evaluation of small intestinal damage, western blot analysis of cyclooxygenase-1 and -2 (COX-1, COX-2) expression, malondialdehyde (MDA), myeloperoxidase (MPO) and prostaglandin E2 (PGE2) levels in small intestine. Indomethacin and diclofenac decreased blood hemoglobin levels, while etoricoxib and celecoxib were without effects. Celecoxib caused a lower degree of intestinal damage, in comparison with the other test drugs. Indomethacin and diclofenac, but not etoricoxib or celecoxib, reduced intestinal PGE2 levels. Test drugs did not modify intestinal COX-1 expression, while they enhanced COX-2, with the exception of celecoxib, which downregulated COX-2. Indomethacin, diclofenac and etoricoxib altered mitochondrial respiratory parameters, while celecoxib was without effects. Indomethacin or diclofenac increased MDA and MPO levels in both jejunum and ileum. In the jejunum, etoricoxib or celecoxib did not modify such parameters, while in the ileum etoricoxib, but not celecoxib, increased both MDA and MPO levels. These findings suggest that non-selective NSAIDs and etoricoxib can induce enteropathy through a topic action, while celecoxib lacks relevant detrimental actions. The selectivity profile of COX-1/COX-2 inhibition by test drugs, and the related effects on prostaglandin production, do not appear to play a major role in the pathogenesis of enteropathy.