Irisin /resveratrol combination ameliorates cisplatin induced acute kidney injury in rats: spotlight on ferroptosis and Nrf2/MIOX pathways | ||
| Bulletin of Egyptian Society for Physiological Sciences | ||
| Articles in Press, Accepted Manuscript, Available Online from 04 November 2025 PDF (1.64 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/besps.2025.407102.1227 | ||
| Authors | ||
| Nesren Mohamed Aboadra* 1; Amr Zidan2; Nancy Nagy Abed El-Hady Ibrahim3; Eman Sobhy Abd Ellatif4; Hadeer Shaker Salah4; Hebatuallah Abedelhaleem Elhabiby5; mayada mohamed azab6 | ||
| 1Medical physiology department Tanta university Faculty of medicine | ||
| 2Medical Pharmacology Department, Faculty of Medicine, Tanta University, Egypt. | ||
| 3Anatomy and Embryology Department Faculty of Medicine, Tanta University | ||
| 4Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Tanta University, Egypt. | ||
| 5Internal Medicine Department, Faculty of Medicine, Tanta University, Egypt. | ||
| 6Physiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt. | ||
| Abstract | ||
| Background & aim: Cisplatin-induced acute kidney injury (AKI) is a serious condition with high morbidity and mortality. This study aimed to investigate the therapeutic role of irisin and resveratrol either individually or in combination in cisplatin-induced AKI focusing on ferroptosis and the potential involvement of nuclear factor erythroid 2–related factor 2 (Nrf2) and Myo-inositol oxygenase (MIOX). Methods: Thirty male Wistar rats were divided into five groups: control, cisplatin, irisin + cisplatin, resveratrol + cisplatin, and combined irisin/resveratrol + cisplatin. AKI was induced by a single intraperitoneal injection of cisplatin (8 mg/kg). Irisin (1 mg/kg) and resveratrol (10 mg/kg) were administered intraperitoneally 30 minutes after cisplatin and again on day three. On day five, blood and kidney tissues were collected for biochemical, histopathological and immunohistochemical assessments of B cell lymphoma 2 apoptosis regulator (Bcl-2). Renal function markers (renal index, serum creatinine and blood urea nitrogen [BUN}), oxidative stress parameters (reduced glutathione [GSH}, malondialdehyde [MDA], glutathione peroxidase [GPX]), inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin 6 [IL-6]), and ferrous iron levels were measured. Gene expression of Nrf2 and MIOX was analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: Treatment with either irisin or resveratrol significantly improved renal function, reduced oxidative stress, inflammation, ferroptosis markers and MIOX expression, while enhancing GPX4 activity, Nrf2, and Bcl-2 expression. While their combination was more pronounced versus each agent alone. Conclusion: The enhanced effect of irisin /resveratrol combination may be attributed to their complementary antioxidant, anti-inflammatory, and anti-apoptotic actions, along with their ability to regulate ferroptosis. | ||
| Keywords | ||
| Irisin; Resveratrol; Cisplatin-induced AKI; Ferroptosis; Nrf2 | ||
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