Tranilast protects from sepsis-induced acute kidney injury in rat via the STAT-3 signaling pathway

Mümin Alper Erdoğan; Arife Erdoğan; Oytun Erbaş

doi:10.18621/eurj.1701524

Tranilast protects from sepsis-induced acute kidney injury in rat via the STAT-3 signaling pathway

Abstract

Objectives: Sepsis-induced acute kidney injury (SI-AKI) is a major contributor to morbidity and mortality among critically ill patients. This experimental study evaluated the renoprotective effects of Tranilast, an anti-inflammatory and antifibrotic agent, in a rat model of polymicrobial sepsis, with a focus on modulation of the signal transducer and activator of transcription 3 (STAT-3) signaling pathway.

Methods: Thirty-six female Wistar albino rats were randomly assigned to three groups: Sham control, cecal ligation and puncture (CLP)+saline, and CLP+Tranilast (300 mg/kg/day). Sepsis was induced by CLP. Survival was monitored for five days. Biochemical parameters including plasma tumor necrosis factor alpha (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL), heat shock protein 27 (HSP-27), malondialdehyde (MDA), blood urea nitrogen (BUN), and renal STAT-3 expression were assessed via ELISA and spectrophotometric assays. Histopathological evaluation of renal tissues was performed to assess tubular injury, inflammation, and hemorrhage. Results are expressed as mean±standard error of the mean (SEM).

Results: Tranilast significantly improved survival in septic rats (75% vs. 50% in CLP+saline), reduced plasma MDA and TNF-α levels, lowered BUN and NGAL concentrations, and suppressed renal STAT-3 expression (P<0.05). It also enhanced HSP-27 levels, suggesting activation of cytoprotective responses. Histological analysis demonstrated reduced tubular necrosis, luminal debris, inflammation, and hemorrhage in Tranilast-treated rats.

Conclusions: Tranilast provides significant renoprotection in SI-AKI by reducing oxidative stress, inflammation, and STAT-3 activity while enhancing cytoprotective mechanisms. These findings support its potential as an adjunctive therapeutic agent for managing sepsis-related organ injury.

Keywords

Ethical Statement

The study protocol was reviewed and approved by the Demiroğlu Science University Animal Experiments Local Ethics Committee (HADYEK) (Decision No: 0825015107; date: 15.02.2023). All experimental procedures involving animals were conducted in accordance with the ethical standards of the Guide for the Care and Use of Laboratory Animals published by the U.S. National Institutes of Health. All efforts were made to minimize animal suffering and to reduce the number of animals used.

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Details

Primary Language

English

Subjects

Physiopathology , Medical Physiology (Other)

Journal Section

Research Article

Authors

Mümin Alper Erdoğan ^*
0000-0003-0048-444X
Türkiye

Arife Erdoğan
0000-0003-2488-2012
Türkiye

Oytun Erbaş
0000-0001-5427-8428
Türkiye

Early Pub Date

August 17, 2025

Publication Date

November 4, 2025

Submission Date

May 18, 2025

Acceptance Date

August 9, 2025

Published in Issue

Year 1970 Volume: 11 Number: 6

DOI

https://doi.org/10.18621/eurj.1701524

IZ

https://izlik.org/JA35HG42RW

Cite

RIS / Bibtex

AMA

1.Erdoğan MA, Erdoğan A, Erbaş O. Tranilast protects from sepsis-induced acute kidney injury in rat via the STAT-3 signaling pathway. Eur Res J. 2025;11(6):1043-1056. doi:10.18621/eurj.1701524