PhD Scientific Days 2026

Poster Session 1.I - Theoretical and Translational Medicine

TLR5 Agonist Therapy Mitigates Indomethacin-Induced Acute Kidney Injury and Autophagy Impairment in Mice

Előadó neve

Haghighi, Samaneh, PhD

Neptune code

KV7P20

Előadó munkahelye

Institute of Clinical Pathophysiology

Előadó telefonszáma

+36704207849

Előadó e-mail címe

samaneh.haghighi@phd.semmelweis.hu

Az előadás címe

TLR5 Agonist Therapy Mitigates Indomethacin-Induced Acute Kidney Injury and Autophagy Impairment in Mice

Szerző(k) neve és munkahelye

Samaneh Haghighi¹, Arezoo Haghighi², Zoltán Zádori², Gábor Kökény¹

1: Institute of Clinical Pathophysiology
2: Department of Pharmacology and Pharmacotherapy

Bemutatás módja

Poszter

Szekció

Poster Session 1.I - Theoretical and Translational Medicine

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Background and Aims
Non-steroidal anti-inflammatory drugs like indomethacin frequently cause acute kidney injury through mechanisms partly independent of COX inhibition, including EGR1 activation and autophagy dysfunction (doi:10.1016/j.yexmp.2025.105000). While TLR5 agonist flagellin has shown protective effects against oxidative stress in ischemic kidney injury, its role in NSAID-induced renal damage remains unexplored. This study investigated the effects of TLR5 agonist treatment on indomethacin-induced acute kidney injury in mice.
Method
Male 8-week-old C57Bl/6J mice were randomly divided into 3 groups: 1) untreated control (CTL, n=7); 2) Indomethacin (IND, 40mg/kg, n=7) and indomethacin+30µg flagellin (IND+F, n=7) treatment, and after 24 hours, the kidneys were processed for histological and molecular studies. ANOVA and Kruskal-Wallis tests were used for statistical evaluation.
Results
The degree of glomerular and tubular damage and inflammatory infiltration was significantly higher in IND than in CTL kidneys (p<0.05), but decreased by 40% in IND+F kidneys (p<0.01). Similarly, Lcn2 (lipocalin-2 or NGAL) mRNA expression was six times higher in IND kidneys than in CTL kidneys, but decreased by 50% in the IND+F group (p<0.05). IND treatment caused a fivefold increase in Ccl2 (MCP-1) expression, which was reduced to a quarter in IND+F kidneys. In parallel, IND treatment caused a fourfold increase in Egr1, fivefold increase in Egr2 and a sevenfold increase in c-Jun mRNA expression, that all returned to untreated control levels in the IND+F group (p<0.05). IND increased sevenfold Lc3b mRNA, twofold LC3II/I protein ratio, and threefold SQSTM1 (p62) protein levels, indicating autophagy dysregulation. Both LC3II/I and SQSTM1 proteins were significantly reduced by 50% in IND+F kidneys (p<0.05).
Conclusion
TLR5 agonist treatment provides renoprotection in this model by suppressing indomethacin-induced inflammatory or pro-fibrotic responses and restoring autophagy flux. Further research is needed to assess therapeutic potential.
Funding
The study was funded by the National Research, Development and Innovation Office, Hungary (NKFI FK138842) and the Tempus Public Foundation, Hungary (Stipendium Hungaricum Fellowship). The author was also supported by the Predoctoral and the SE 250+ Excellence Scholarship.

University

Semmelweis University

Supervisor

Dr. Gabor Kokeny

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

after finishing doctoral studies with absolutorium (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7371

Start

16:30

End

16:33