Therapeutic Effects of Alpha-Lipoic Acid on High-Dose Ibuprofen-Induced Renal Damage in Rats

Halime Tozak Yıldız

doi:10.18621/eurj.1785523

Therapeutic Effects of Alpha-Lipoic Acid on High-Dose Ibuprofen-Induced Renal Damage in Rats

Abstract

Objectives: Nonsteroidal anti-inflammatory drugs, particularly ibuprofen, are commonly used worldwide and can cause nephrotoxicity through prostaglandin inhibition, oxidative stress, and inflammatory activation. This study aimed to investigate the histopathological, fibrotic, and oxidative effects of high-dose ibuprofen administration and to evaluate the therapeutic potential of alpha-lipoic acid) in reversing these changes.

Methods: Twenty-eight male Wistar albino rats were randomly divided into four groups (n=7): Control, Alpha-lipoic acid (100 mg/kg), Ibuprofen (250 mg/kg), and Ibuprofen+Alpha-lipoic acid. Ibuprofen was administered orally for 21 days, while alpha-lipoic acid was given during the last 7 days. Histopathological changes were evaluated using Hematoxylin & Eosin, Masson’s Trichrome, and Periodic Acid–Schiff staining. Fibrotic and inflammatory markers (TGF-β1, α-SMA, TLR-4) were assessed immunohistochemically. Oxidative stress was evaluated by measuring malondialdehyde levels and superoxide dismutase activity.

Results: Ibuprofen administration resulted in significant tubular degeneration, hydropic changes, necrosis, tubular dilatation, and hyperemia. Masson’s Trichrome staining showed a significant increase in collagen deposition, while Periodic Acid-Schiff staining revealed glomerular and tubular basement membrane thickening. Immunohistochemistry demonstrated marked upregulation of TGF-β1, α-SMA, and TLR-4 (P<0.001). Biochemically, malondialdehyde levels were significantly increased (P<0.01) and superoxide dismutase activity was markedly decreased (P<0.001) compared to controls. Alpha-lipoic acid treatment significantly ameliorated these changes, reducing fibrosis and inflammatory marker expression and restoring malondialdehyde and superoxide dismutase levels toward normal (P<0.05).

Conclusions: Alpha-lipoic acid exerts renoprotective effects against ibuprofen-induced nephrotoxicity by reducing oxidative stress, modulating fibrotic pathways, and improving renal histoarchitecture, suggesting its potential as a therapeutic agent in drug-induced kidney injury.

Keywords

Ethical Statement

This study was approved by the Kırşehir Ahi Evran University Animal Experiments Local Ethics Committee (Decision No: 08/4; date: 24.04.2025). 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

Nefroloji, Pathology

Journal Section

Research Article

Authors

Halime Tozak Yıldız ^*
0000-0003-4310-6238
Türkiye

Early Pub Date

December 24, 2025

Publication Date

February 1, 2026

Submission Date

September 17, 2025

Acceptance Date

October 30, 2025

Published in Issue

Year 2026 Volume: 12 Number: 2

DOI

https://doi.org/10.18621/eurj.1785523

IZ

https://izlik.org/JA87PP78ZF

Cite

RIS / Bibtex

APA

Tozak Yıldız, H. (2026). Therapeutic Effects of Alpha-Lipoic Acid on High-Dose Ibuprofen-Induced Renal Damage in Rats. The European Research Journal, 12(2), 149-159. https://doi.org/10.18621/eurj.1785523

AMA

1.Tozak Yıldız H. Therapeutic Effects of Alpha-Lipoic Acid on High-Dose Ibuprofen-Induced Renal Damage in Rats. Eur Res J. 2026;12(2):149-159. doi:10.18621/eurj.1785523

Chicago

Tozak Yıldız, Halime. 2026. “Therapeutic Effects of Alpha-Lipoic Acid on High-Dose Ibuprofen-Induced Renal Damage in Rats”. The European Research Journal 12 (2): 149-59. https://doi.org/10.18621/eurj.1785523.

EndNote

Tozak Yıldız H (February 1, 2026) Therapeutic Effects of Alpha-Lipoic Acid on High-Dose Ibuprofen-Induced Renal Damage in Rats. The European Research Journal 12 2 149–159.

IEEE

[1]H. Tozak Yıldız, “Therapeutic Effects of Alpha-Lipoic Acid on High-Dose Ibuprofen-Induced Renal Damage in Rats”, Eur Res J, vol. 12, no. 2, pp. 149–159, Feb. 2026, doi: 10.18621/eurj.1785523.

ISNAD

Tozak Yıldız, Halime. “Therapeutic Effects of Alpha-Lipoic Acid on High-Dose Ibuprofen-Induced Renal Damage in Rats”. The European Research Journal 12/2 (February 1, 2026): 149-159. https://doi.org/10.18621/eurj.1785523.

JAMA

1.Tozak Yıldız H. Therapeutic Effects of Alpha-Lipoic Acid on High-Dose Ibuprofen-Induced Renal Damage in Rats. Eur Res J. 2026;12:149–159.

MLA

Tozak Yıldız, Halime. “Therapeutic Effects of Alpha-Lipoic Acid on High-Dose Ibuprofen-Induced Renal Damage in Rats”. The European Research Journal, vol. 12, no. 2, Feb. 2026, pp. 149-5, doi:10.18621/eurj.1785523.

Vancouver

1.Halime Tozak Yıldız. Therapeutic Effects of Alpha-Lipoic Acid on High-Dose Ibuprofen-Induced Renal Damage in Rats. Eur Res J. 2026 Feb. 1;12(2):149-5. doi:10.18621/eurj.1785523