Effect of Ketoprofen and ATB-352 on the Immature Human Intestine: Identification of Responders and Non-Responders

Journal of Pediatric Gastroenterology and Nutrition
Marie-Pier ThibaultJean-François Beaulieu

Abstract

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a broad spectrum of life-threatening adverse effects on the immature gastrointestinal tract. NSAID derivatives exploiting the beneficial effects of biologically active gases, such as hydrogen sulfide (H2S), have been developed. Herein, we determined the effects of ketoprofen and ATB-352, a H2S-releasing ketoprofen derivative, on selected metabolic pathways previously identified to be significantly altered by indomethacin in the human immature intestine. Ketoprofen and ATB-352 were tested on human mid-gestation small intestinal explants maintained in a serum-free organ culture system for 48 h. The expression levels of the representative genes involved in selected metabolic pathways were measured by real-time PCR after a treatment of 48 hours. Tested at a concentration that allows more than 80% inhibition of PGE2 production, ketoprofen was found to be less damaging than indomethacin at an equivalent dosage. However, based on the inducibility of cyclooxygenase-2 transcript expression, we were able to discriminate between responder individuals in which the deleterious effects observed with indomethacin were attenuated, and non-responder specimens in which t...Continue Reading

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