Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Roxadustat protects rats from cisplatin-induced acute kidney injury

Cuneyt Ar?kan¹ , Ejder Saylav Bora², Duygu Burcu Arda³, Oytun Erbas⁴

¹Department of Emergency Medicine, Faculty of Medicine, Dokuz Eylül University, Turkey; ²Department of Emergency Medicine, Atatürk Training and Research Hospital, ?zmir, Turkey; ³Department of Pediatrics, Gaziantep University, Gaziantep, Turkey; ⁴Department of Physiology, Demiroglu Bilim University, Istanbul, Turkey.

For correspondence:- Cuneyt Ar?kan Email: cuneyt.arikan@deu.edu.tr

Accepted: 8 July 2024 Published: 31 July 2024

Citation: Ar?kan C, Bora ES, Arda DB, Erbas O. Roxadustat protects rats from cisplatin-induced acute kidney injury. Trop J Pharm Res 2024; 23(7):1077-1082 doi: 10.4314/tjpr.v23i7.5

© 2024 The authors.
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Abstract

Purpose: To investigate the potential protective effect of roxadustat against cisplatin-induced acute kidney injury (AKI) by evaluating biochemical markers, inflammatory parameters, renal function tests, and histopathological changes.

Methods: Thirty female Wistar rats were randomized into control group, cisplatin with tap water group, and cisplatin with roxadustat group. Cisplatin-induced AKI was established by intraperitoneal injection of cisplatin at 10 mg/kg for seven days. Roxadustat was administered orally at 20 mg/kg/day to the treatment group. Blood and kidney samples were collected for biochemical and histopathological analyses respectively.

Results: Roxadustat treatment significantly reduced markers of renal injury (malondialdehyde (MDA), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), transforming growth factor-beta 1 (TGF-beta1)), inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18)) compared to the cisplatin group (p < 0.005). In addition, roxadustat treatment also improved renal function (blood urea nitrogen (BUN), serum creatinine (SCr)) compared to the cisplatin group (p < 0.005). Histopathological examination revealed a significant decrease in tubular epithelial necrosis and luminal necrotic debris in the roxadustat-treated group (p < 0.005). However, there was no significant difference in tubular dilatation and interstitial inflammation between groups (p > 0.05).

Conclusion: Roxadustat significantly prevents cisplatin-induced AKI by attenuating renal injury, reducing inflammation, and improving renal function. This evidence suggests that roxadustat may be a promising preventive option for patients receiving cisplatin chemotherapy.

Keywords: Roxadustat, FG-4592, Cisplatin, Acute kidney injury