Renoprotective effect of Limonium duriusculum (de Girard) Kuntze via modulation of oxidative stress/ UPR markers and inflammation during cyclosporine-induced nephrotoxicity in rats
نویسندگان
1 Laboratoire de Biologie et Environnement, Faculté des Sciences de la Nature et de la Vie, Université Frères Mentouri Constantine 1, Route Aïn El Bey, 25000, Constantine, Algérie
2 Unité de Recherche, Valorisation des Ressources Naturelles, Molécules Bioactives et Analyses Physicochimiques et Biologiques (VARENBIOMOL), Université Frères Mentouri, Constantine 1, Route Aïn El Bey, 25 000 Constantine, Algérie
3 Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, Madrid, Spain
4 Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Warsaw, Poland
5 Laboratoire de Biologie et Environnement, Faculté des Sciences de la Nature et de la Vie, Université Frères Mentouri Constantine 1, Route Aïn El Bey, 25000, Constantine, Algérie
6 Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Warsaw, Poland
7 Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, Madrid, Spain
8 Laboratoire de Biologie et Environnement, Faculté des Sciences de la Nature et de la Vie, Université Frères Mentouri Constantine 1, Route Aïn El Bey, 25000, Constantine, Algérie
doi
10.22038/ijbms.2024.77052.16661چکیده
Objective(s): The present study aimed to explore the mechanisms underlying the potency of the renoprotective effect of the EtOAc fraction of Limonium duriusculum (EALD) (Plumbaginaceae) against cyclosporine A (CsA), in comparison to vitamin E (Vit. E).Materials and Methods: In the in-vivo 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 in-vitro 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 L. duriusculum, as it demonstrated the ability to ameliorate CsA-induced renal dysfunction through its distinctive antioxidant properties.
