PhD Scientific Days 2023

Pharmaceutical Sciences - Posters F

Drug and Dose-dependent Tissue Injury in the Rat Renal Medulla after Chronic Treatment with NSAIDs

Előadó neve

Haghighi, Samaneh, PhD

Neptun code

KV7P20

Előadó munkahelye

Institute of Translational Medicine

Előadó telefonszáma

+36704207849

Előadó e-mail címe

haghighi_samane@yahoo.com

Az előadás címe

Drug and Dose-dependent Tissue Injury in the Rat Renal Medulla after Chronic Treatment with NSAIDs

Szerző(k) neve és munkahelye

1 Samaneh Haghighi, Institute of Translational Medicine, Budapest
2 Arezoo Haghighi, Department of Pharmacology and Pharmacotherapy, Budapest
3 Zoltán S. Zádori, Department of Pharmacology and Pharmacotherapy, Budapest
4 Gábor Kökény1, Institute of Translational Medicine/International Nephrology Research and Training Center, Budapest

Bemutatás módja

Poszter

Szekció

Pharmaceutical Sciences - Posters F

Language of the presentation

English

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively in clinical medicine. Chronic NSAID use is known to reduce renal medullary blood flow thus might lead to severe and irreversible damage and papilla necrosis. Non-selective NSAIDs were reported to induce mitochondrial dysfunction and renal damage in rats. Since renal tubular epithelial cells are one of the most ATP demanding cell types of the body, alterations in mitochondria have been recognized as a hallmark of the initiation and progression of several kidney diseases. Moreover, chronic damage to the renal medulla increases the expression of pro-fibrotic EGR1 and TGF-beta1 . Sirtuin 3 (SIRT3) plays pivotal role in maintaining mitochondrial homeostasis and mitochondrial dysfunction with altered SIRT3 expression has been described in experimental acute kidney injury. Yet, the possible renal effects of chronic NSAID treatment on SIRT3 and pro-fibrotic factors haven’t been investigated.
Aim: Histological and gene expression analysis of renal cortex and medulla after chronic NSAID treatment.
Methods: Non-fasted male Wister rats were treated twice daily orally for two weeks with different NSAIDs as follows: indomethacin (2 mg/kg), naproxen (10 or 20 mg/kg), celecoxib (10 and 30 mg/kg) or vehicle (1% hydroxyethylcellulose). Kidneys were removed, the left kidneys were used for histology while right kidney cortex and medulla were separated and snap frozen. Histological damage scores were evaluated on PAS-stained slides according to El Nahas et al, assessing tubular dilatation, epithelial atrophy and mononuclear cell infiltration. Total mRNA was isolated from cortex and medulla, and gene expression of SIRT3, EGR1 and TGF-beta1 were assessed by qPCR.
Results: Chronic treatment of NSAIDs caused tubular dilatation significantly in rat’s kidney in all NSAIDs treated group except for indomethacin 2 mg/kg in histological analysis. Also, a significant increase in histological epithelial atrophy was confirmed for celecoxib 10, 30 and naproxen 10 mg/kg. This is while that mononuclear cell infiltration increased significantly just in celecoxib 10 mg/kg. Gene expression analysis is on progress.
Conclusion: Here we characterize the dose-dependent tissue injury in the rat renal medulla after chronic treatment with different NSAIDs for the first time. Whether these changes contribute to NSAIDs -induced renal tissue injury remains to be elucidated.

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine

Other university and doctoral school, not listed above

Semmelweis University, Department of Pharmacology and Pharmacotherapy

Supervisor

Gábor Kökény

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

12:06

End

12:11

Authors (legacy)

1 Samaneh Haghighi, Institute of Translational Medicine, Budapest
2 Arezoo Haghighi, Department of Pharmacology and Pharmacotherapy, Budapest
3 Zoltán S. Zádori, Department of Pharmacology and Pharmacotherapy, Budapest
4 Gábor Kökény1, Institute of Translational Medicine/International Nephrology Research and Training Center, Budapest