PhD Scientific Days 2021

PH_II_P: Pharmaceutical Sciences II. Posters

Analysing the Effect of the Alpha-2 Adrenoceptor Agonist Clonidine on 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. Our previous studies have demonstrated that alpha-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 alpha-2 adrenoceptor agonist clonidine on NSAID-induced enteropathy in an animal model.
Methods: Male Wistar rats (180-220 g) were treated with clonidine (10 and 100 microgram/kg) or its 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 measuring serum parameters and intestinal inflammatory markers.
Results: Indomethacin-induced enteropathy was associated with shortening of the small bowel, elevation of intestinal myeloperoxidase and interleukin 1β, and with severe blood loss, and serum protein loss. Clonidine treatment had no significant effect on any of the tested parameters.
Conclusion: Our results suggest that pharmacological stimulation of alpha-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 studies with other alpha-2 adrenoceptor agonists are required to confirm the present findings.
Funding: OTKA 124878, and EFOP-3.6.3-VEKOP-16-2017-00009

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences