PhD Scientific Days 2022

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

The role of the lysophosphatidic acid 2 (LPA2) receptor in gastropathy caused by non-steroidal anti-inflammatory drugs

Előadó neve

Hutka, Barbara, MSc

Előadó munkahelye

Semmelweis University, Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

+36305412520

Előadó e-mail címe

hutka.barbara@semmelweis-univ.hu

Az előadás címe

The role of the lysophosphatidic acid 2 (LPA2) receptor in gastropathy caused by non-steroidal anti-inflammatory drugs

Szerző(k) neve és munkahelye

Barbara Hutka1, Mahmoud Al-Khrasani1, Klára Gyires1, Zoltán S. Zádori1

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
The role of the lysophosphatidic acid 2 (LPA2) receptor in the gastrointestinal tract has not been sufficiently elucidated, and both protective and detrimental effects have been described in various animal models. Our previous results suggest that low receptor activation attenuates intestinal damage caused by indomethacin, a non-steroidal anti-inflammatory drug (NSAID), whereas overstimulation is already associated with increased intestinal inflammation. The effect of the LPA2 receptor on NSAID-induced gastric ulceration has hardly been investigated.

Aims
Investigation of the effect of the LPA2 receptor agonist DBIBB and the antagonist H2L5186303 on indomethacin-induced gastric damage and inflammation.

Methods
In our experiments, Wistar rats were treated intragastrically with different doses of the LPA2 receptor agonist DBIBB and the receptor antagonist H2L5186303 (0.01 - 10 mg/kg) or with their solvent twice, 23 and a half hours apart. Thirty minutes after the last treatment, the animals received indomethacin (30 mg/kg), and 6 hours later, the extent of ulcers was examined. In our next experiment, we examined the effect of DBIBB on C57BL/6 mice according to the protocol describe previously. The animals received 40 mg/kg indomethacin and after 24 hours the tissue inflammation was determined by Western blot.

Results
In Wistar rats, DBIBB at a dose of 1 mg/kg reduced the extent of indomethacin-induced ulcer area, but at a dose of 10 mg/kg it increased it. The 0.1 mg/kg dose of H2L5186303 increased the extent of the ulcer area caused by indomethacin, whereas at the other two doses had no significant effect on it. In mice, the 1 mg/kg dose of DBIBB did not yet affect gastric tissue inflammation, but the 10 mg/kg dose reduced the tissue levels of both myeloperoxidase and cyclooxygenase-2.

Conclusion
Based on our results, low stimulation of the LPA2 receptor can reduce indomethacin-induced epithelial damage and tissue inflammation in the stomach. However, higher doses of DBIBB may already exacerbate gastric damage. On the other hand, receptor inhibition exacerbates epithelial damage. Further experiments are planned to clarify the mechanisms underlying the observed effects.

Funding
NKFI FK 138842, ÚNKP-21-3-II-SE-33, EFOP-3.6.3-VEKOP-16-2017-00009

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Dr. 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

6812

Start

10:20

End

10:25

Authors (legacy)

Barbara Hutka1, Mahmoud Al-Khrasani1, Klára Gyires1, Zoltán S. Zádori1

1 Semmelweis University, Department of Pharmacology and Pharmacotherapy, Budapest