PhD Scientific Days 2023

Molecular Sciences II.

Protective effects of Sigma-1 Receptor Agonists in Renal Ischemia/Reperfusion Injury

Előadó neve

Toth, Akos Roland

Neptun code

AUWTRH

Előadó munkahelye

Semmelweis University, Pediatrics Center, Budapest

Előadó telefonszáma

+36706604784

Előadó e-mail címe

akostoth95@gmail.com

Az előadás címe

Protective effects of Sigma-1 Receptor Agonists in Renal Ischemia/Reperfusion Injury

Szerző(k) neve és munkahelye

Akos Toth1,2; Judit Hodrea1,2; Dora Bianka Balogh1,2; Attila J. Szabo2; Andrea Fekete1, 2; Adam Hosszu1,2

1MTA-SE Lendület ˝Momentum˝ Diabetes Research Group, Budapest, Hungary
2Semmelweis University Pediatrics Center, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Molecular Sciences II.

Language of the presentation

English

Preferred session

Molecular Sciences

Összefoglaló szövege

Introduction
Renal ischemia/reperfusion injury (IRI)-induced acute kidney injury is associated with high mortality and morbidity and effective therapies are lacking. We previously showed that Sigma-1 receptor (S1R) agonist fluvoxamine treatment is protective against renal IRI through anti-inflammatory effects and improving renal perfusion.
Aims
The aim of the study was to investigate the renoprotective effect of specific, high affinity S1R agonists focusing on the S1R-Akt-eNOS signaling pathway and renal vasoregulation.
Methods
8 week-old male Wistar rats (n=8/group) were subjected to 50 min of unilateral ischemia with contralateral nephrectomy. 30 min before to the ischemic insult rats were treated intraperitoneally as follows: (i) isotonic saline as vehicle; (ii) highly specific, high affinity S1R agonist SA-4503 (SA); (iii) SA+ S1R antagonist NE100. Sham-operated rats were used as controls. Samples were collected 24 hours after reperfusion. Highly selective tubular injury markers (Kim1, Ngal) gene expression were evaluated. Periodic-Acid Schiff (PAS) staining was performed on kidney tissue sections to determine structural damage. Renal S1R, phospho-Akt and phospho-eNOS, Hif-1α protein levels and serum nitric oxide (NO) concentration were measured.
Results
Renal functional parameters, blood urea nitrogen (BUN) and serum aspartate aminotransferase (AST) were reduced in the SA treated group. Expressions of sensitive tubular injury markers Kim1 and Ngal were less elevated in SA-treated rats. 24h after reperfusion. S1R, phospho-Akt and phospho-eNOS protein levels were significantly elevated in the kidneys of SA treated rats. Vasodilator nitric oxide concentration was reduced in the kidney after IRI, but returned to control levels in SA treated rats.
Conclusion
The specific and high affinity S1R agonist SA-4503 acts directly on proximal tubular cells by activating the S1R-NOS system. SA-4503 is renoprotective by increasing vasodilative NO production and thus improving post-ischemic renal perfusion. Based on our results activation of S1R and downstream signaling pathways could provide a novel therapeutic option in renal IRI.
Funding: OTKA PD-131637; LP2021-3/2021, PC2022-8/2022; TKP2021-EGA-24

University and Doctoral School

Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine

Supervisor

Dr. Adam Hosszu

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

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4764

Start

15:30

End

15:45

Authors (legacy)

Akos Toth1,2; Judit Hodrea1,2; Dora Bianka Balogh1,2; Attila J. Szabo2; Andrea Fekete1, 2; Adam Hosszu1,2

1MTA-SE Lendület ˝Momentum˝ Diabetes Research Group, Budapest, Hungary
2Semmelweis University Pediatrics Center, Budapest, Hungary