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

Előadó neve

Dr. Tóth, András Sebestyén

Előadó munkahelye

Semmelweis University Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

+36307010772

Előadó e-mail címe

tothiska@gmail.com

Az előadás címe

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

Szerző(k) neve és munkahelye

András Tóth1, Barbara Hutka1, Patrik Pálnok1, Mahmoud Al-Khrasani1, Klára Gyires, Zoltán S. Zádori
1 Semmelweis University, Department of Pharmacology and Pharmacotherapy, Budapest

Bemutatás módja

Poszter

Szekció

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

Language of the presentation

Hungarian

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

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

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Zoltán S. Zádori

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6820

Start

10:30

End

10:35

Authors (legacy)

András Tóth1, Barbara Hutka1, Patrik Pálnok1, Mahmoud Al-Khrasani1, Klára Gyires, Zoltán S. Zádori
1 Semmelweis University, Department of Pharmacology and Pharmacotherapy, Budapest