PhD Scientific Days 2022

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

Alpha-2 adrenoceptor agonists failed to alleviate indomethacin-induced small bowel damage in rats

Text of the abstract

Introduction: It is increasingly recognized that non-steroidal anti-inflammatory drugs (NSAIDs) induce significant damage to the small intestine, with the prevalence rate of mucosal breaks of around 50% in chronic users. The development of small intestinal injury does not depend on acid secretion, but, instead, on other factors, including enteric bacteria, bile acids, prostaglandin deficiency and topical damaging effects. Since there is no well-established prophylactic approach, there is an urgent need to discover agents, that could prevent NSAID enteropathy. Besides others, our previous studies have also demonstrated that 2 adrenoceptor agonists induce protective effect in the stomach by multiple mechanisms. However, little is known about the effect of these medications on NSAID enteropathy.
Aims: To assess the effects of the 2 adrenoceptor agonist (clonidine and dexmedetomidine) on NSAID-induced enteropathy in an animal model.
Methods: Male Wistar rats (180-220 g) were treated with clonidine (10 and 100 g/kg) or dexmedetomidine (5 és 50 g/kg) or their vehicle (distilled water) per os twice daily for 3 days. NSAID enteropathy was induced by a single dose of indomethacin (20 mg/kg), given per os on day 2. On day 4, rats were euthanized, and the severity of enteropathy was evaluated by histological analyses; by measuring inflammatory marker levels in the bowel wall; and by assessing the extent of blood and serum protein loss .
Results: Indomethacin-induced enteropathy was associated with shortening of the small bowel (as a result of inflammation), elevation of inflammatory markers (myeloperoxidase, pentraxin-3, cathelicidin), in the intestinal wall, and with severe blood loss, and serum protein loss. Neither Clonidine nor Dexmedetomidine treatment could alleviate these changes, moreover the higher dose of dexmedetomidine deteriorated some parameters.
Conclusion: Our results suggest that pharmacological stimulation of 2 adrenoceptors cannot prevent NSAID-induced entropathy, despite its well-established gastroprotective effect. This may be due to the different pathogenesis of gastro- and enteropathy. But further investigations are needed to elucidate the background of their dissimilar behaviour in different gastrointestinal regions..
Funding: OTKA 124878, NKFI FK 138842, and EFOP-3.6.3-VEKOP-16-2017-00009