PhD Scientific Days 2024

Poster Session H - Theoretical and Translational Medicine 1.

Unraveling the Impact of NSAIDs on Kidney Function: Autophagy, Fibrosis, and Dose-Dependent Morphological Insights

Előadó neve

Haghighi, Samaneh, PhD

Neptun code

kv7p20

Előadó munkahelye

translational medicine

Előadó telefonszáma

06704207849

Előadó e-mail címe

haghighi_samane@yahoo.com

Az előadás címe

Unraveling the Impact of NSAIDs on Kidney Function: Autophagy, Fibrosis, and Dose-Dependent Morphological Insights

Szerző(k) neve és munkahelye

Samaneh Haghighi¹

1: translational medicine

Bemutatás módja

Poszter

Szekció

Poster Session H - Theoretical and Translational Medicine 1.

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Background: NSAIDs, widely used for managing inflammation, pain, and fever, inhibit COX enzymes to decrease prostaglandin synthesis. While beneficial, they may negatively affect renal health by inducing nephrotoxic effects. NSAID use is also linked to mitochondrial dysfunction and oxidative stress, which contribute to renal damage and fibrosis through pro-fibrotic factors like TGF-β and EGR1. Kidney injuries could disrupt autophagy, leading to diminished cellular repair and increased fibrosis. However, the specific impacts of NSAIDs on renal autophagy remain unexplored.
Aim: Our study aims to clarify NSAID effects on renal pro-fibrotic signaling and autophagy, assessing histological damage to understand the underlying pathology.
Methods: Male Wistar rats received oral doses of indomethacin (2 mg/kg), naproxen (10 or 20 mg/kg), celecoxib (10 and 30 mg/kg), or a control solution twice daily for two weeks. We conducted histological assessments on the left kidney and molecular analyses (qPCR and immunoblotting) on the right kidney cortex and medulla.
Results: NSAIDs, particularly Celecoxib and Naproxen, cause dose-dependent renal morphology changes, including increased tubular dilatation and atrophy. High doses of these NSAIDs significantly elevate Egr1 expression in both the renal cortex and medulla, highlighting a drug and dose-specific impact. In the renal cortex, pro-fibrotic Tgfb1 gene expression was generally reduced, while Naproxen and Celecoxib increased Egr1 and Timp1, respectively. Contrastingly, in the medulla, these NSAIDs elevate Egr1, Timp1, cJun, and Tgfb1, illustrating a nuanced interaction between NSAID concentration and the modulation of pro-fibrotic genes. Immunoblot analyses indicate enhanced autophagy initiation, as shown by raised LC3-I levels and the LC3-II/I ratio, but the concurrent increase in SQSTM1 (p62) levels suggest disrupted autophagic degradation. These findings highlight the complex role of NSAIDs in modulating kidney damage through distinct changes in pro-fibrotic signaling and autophagy pathways.
Conclusion: Celecoxib and Naproxen show significant, dose-dependent impacts on renal morphology and biological markers, highlighting a critical balance between NSAID benefits and renal risks. Our study supports cautious NSAID use and emphasizes the importance of further research to optimize NSAID therapy and reduce renal side effects.

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.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7371

Start

14:45

End

14:48