PhD Scientific Days 2026

Pharmaceutical Sciences and Health Technologies 2.

Investigation of the Role of Endocannabinoids in Indomethacin-Induced Enteropathy in Mice

Előadó neve

Zsuzsanna, Demeter

Neptune code

C3UGZC

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy, Semmelweis University

Előadó telefonszáma

06709417195

Előadó e-mail címe

demeter.zsuzsanna@semmelweis.hu

Az előadás címe

Investigation of the Role of Endocannabinoids in Indomethacin-Induced Enteropathy in Mice

Szerző(k) neve és munkahelye

Zsuzsanna O. Demeter^1,2, Gerda Wachtl^1,2, Arezoo Haghighi^1,2, Anna Zsidai^1,2, Lili Lengyel^1,2, Julian Steinhardt^1,2, Maximilian Manger^1,2, Klára Gyires^1,2, Zoltán S. Zádori^1,2

1: Department of Pharmacology and Pharmacotherapy, Semmelweis University Hungary
2: Center for Pharmacology and Drug Research & Development, Semmelweis University, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Pharmaceutical Sciences and Health Technologies 2.

Language of the presentation

Hungarian

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) frequently leads to damage of the distal small intestine, for which no effective therapy is currently available. The endocannabinoid system (ECS) plays a crucial role in maintaining gastrointestinal homeostasis. In our previous studies, increasing the levels of the two main endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), attenuated NSAID-induced gastric injury. However, inhibition of AEA metabolism with URB597 did not reduce the severity of NSAID-induced enteropathy.
The aim of this study was to determine whether inhibition of monoacylglycerol lipase (MAGL)—a key enzyme involved in 2-AG metabolism—or direct administration of AEA could alleviate indomethacin (IND)-induced enteropathy in mice.
C57BL/6 mice were treated with a single high dose of IND (30 mg/kg p.o.) or its vehicle (1% hydroxyethylcellulose). In the first experiment, animals received JZL184 (4 or 16 mg/kg p.o.) or its vehicle, while in the second experiment mice were treated with AEA (1 or 10 mg/kg p.o.), administered three times. Twenty-four hours after IND treatment, animals were sacrificed, and small intestinal length was measured. Tissue levels of inflammatory mediators and tight junction (TJ) proteins were determined, and AEA and 2-AG concentrations were quantified by LC–MS.
JZL184 treatment significantly increased 2-AG levels in the small intestine, as expected, but did not affect the severity of enteropathy. In contrast, AEA treatment significantly reduced the tissue levels of inflammatory mediators (COX-2, MPO, IL-1β) in enteropathic animals.
Our findings suggest that inhibition of endocannabinoid metabolism alone is not sufficient to alleviate NSAID-induced enteropathy. However, direct administration of AEA significantly reduces intestinal inflammation and may represent a promising therapeutic approach for the treatment of enteropathy. Further studies are needed to clarify the mechanisms underlying the lack of efficacy of metabolism inhibitors.
Grant: NKFI FK 138842

University

Semmelweis University

Supervisor

Zoltán Zádori

Publication of my abstract

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

phd.section.field

in doctoral studies before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

jóváhagyta

Előadó

8929

Start

10:30

End

10:40