PhD Scientific Days 2025

Poster Session III. - H: Pharmaceutical Sciences and Health Technologies

Dose-Dependent Effects of NSAIDs on Autophagy and Oxidative Stress in Human Renal Epithelial Cells

Előadó neve

Haghighi samaneh, PhD

Neptun code

KV7P20

Előadó munkahelye

Semmelweis university

Előadó telefonszáma

0670407849

Előadó e-mail címe

haghighi_samane@yahoo.com

Az előadás címe

Dose-Dependent Effects of NSAIDs on Autophagy and Oxidative Stress in Human Renal Epithelial Cells

Szerző(k) neve és munkahelye

Samaneh Haghighi¹, Arezoo Haghighi², Zoltán S. Zádori², Julianna Pollok¹, Anna Manzéger¹, Gábor Kökény¹

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

Bemutatás módja

Poszter

Szekció

Poster Session III. - H: Pharmaceutical Sciences and Health Technologies

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory properties but have been associated with nephrotoxicity. Previous studies, including our research on rats, demonstrated NSAID-induced kidney damage via oxidative stress, fibrosis, and autophagy dysregulation. This study extends our investigation to in vitro models, focusing on human renal proximal tubular epithelial cells (HK-2) to elucidate NSAID-induced cellular responses.
Aims
This study aims to investigate the dose-dependent effects of NSAIDs on oxidative stress, fibrosis markers, and autophagy regulation in human renal epithelial cells.
Methods
HK-2 cells were treated with indomethacin (10, 20, 40 µg/mL), celecoxib (0.72, 2.1, 4.3, 8.7 µg/mL), naproxen (15, 30, 60, 110 µg/mL), or DMSO (control) for 24 hours. Molecular and biochemical analyses were performed to assess fibrosis markers (Tgfb1, Acta2), autophagy indicators (LC3-II/I ratio, p62), and oxidative stress responses (HO-1, pAKT/AKT ratio). Statistical analysis was conducted using ANOVA or Kruskal-Wallis tests.
Results
High doses of NSAIDs significantly increased oxidative stress and fibrosis markers. Naproxen (NAP110) and celecoxib (CEL8.7) upregulated Tgfb1 (2.2-fold, 2-fold), Acta2 (1.6-fold, 2.2-fold), and Egr1 (2.2-fold, 2.3-fold), accompanied by autophagy disruption evidenced by increased LC3-II/I ratios (2.3-fold, 2.1-fold) and p62 accumulation (4.4-fold, 4.7-fold). HO-1 (2.8-fold, 2.2-fold) and pAKT/AKT (8-fold, 10-fold) levels were significantly elevated in high-dose groups, suggesting a stress-induced compensatory response.
Conclusion
These findings indicate that NSAIDs, particularly at high doses, induce oxidative stress, impair autophagy, and activate pro-fibrotic pathways in human renal epithelial cells. Understanding these mechanisms may aid in optimizing NSAID dosing and developing strategies to mitigate nephrotoxicity.
Funding
SE250+ grant

University

Semmelweis University

Supervisor

Gábor Kökény

Publication of my abstract

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

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7371

Start

14:06

End

14:12