Renoprotective Effect of (de Girard) Kuntze Via Modulation of Oxidative Stress/ UPR Markers and Inflammation During Cyclosporine-induced Nephrotoxicity in Rats

Overview

Journal Iran J Basic Med Sci

Publisher Mashhad University of Medical Sciences

Specialty General Medicine

Date 2024 Jun 24

PMID 38911250

Authors

Azzedine Redouane-Salah

Ameddah Souad

Wafa Kerkatou

Kamil Wojnicki

Adrian M Ramos

Alberto Ortiz

Bozena Kaminska

Ahmed Menad

Affiliations

Soon will be listed here.

Abstract

Objectives: The present study aimed to explore the mechanisms underlying the potency of the renoprotective effect of the EtOAc fraction of (EALD) (Plumbaginaceae) against cyclosporine A (CsA), in comparison to vitamin E (Vit. E).

Materials And Methods: In the experiment, a model of CsA-induced nephrotoxicity was established by dosing male Wistar rats with 25 mg/kg, for 14 days. The protective effect of EALD was investigated through pretreatment of rats with a dose of 200 mg/kg for 14 days, compared to the oral administration of Vit. E at 100 mg/kg. Renal function and markers of oxidative stress were then assessed. Furthermore, a complementary study was carried out to evaluate CsA-induced endoplasmic reticulum stress (ERS) and inflammation on cell culture (3T3 cells and MCT cells) using western blot and quantitative RT-PCR..

Results: Pretreatment of rats with EALD significantly attenuated the elevated levels of renal dysfunction markers (BUN, creatinine) and suppressed malondialdehyde (MDA) levels; It also significantly regulated the changes in superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxydase (GPx), and glutathione S-transferase (GST) levels as compared to Vit. E, demonstrating a more effective recovery in renal tissues. Treatment of cells with CsA was linked to the expression of ERS and inflammatory markers activating transcription factor (ATF4), inositol-requiring enzyme 1α (IRE1α), binding immunoglobulin protein (BiP), and monocyte chemoattractant protein-1 (MCP1). In contrast, pretreatment of cells with EALD resulted in a significant decrease in both ERS and inflammatory markers.

Conclusion: These findings indicate the renoprotective potential of , as it demonstrated the ability to ameliorate CsA-induced renal dysfunction through its distinctive antioxidant properties.

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