Roxadustat protects rats from cisplatin-induced acute kidney injury

被引:1
作者
Arikan, Cuneyt [1 ]
Bora, Ejder Saylav [2 ]
Arda, Duygu Burcu [3 ]
Erbas, Oytun [4 ]
机构
[1] Dokuz Eylul Univ, Fac Med, Dept Emergency Med, Izmir, Turkiye
[2] Ataturk Training & Res Hosp, Dept Emergency Med, Izmir, Turkiye
[3] Gaziantep Univ, Dept Pediat, Gaziantep, Turkiye
[4] Demiroglu Bilim Univ, Dept Physiol, Istanbul, Turkiye
关键词
Roxadustat; FG-4592; Cisplatin; Acute kidney injury; ANEMIA;
D O I
10.4314/tjpr.v23i7.5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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-alpha), 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.
引用
收藏
页码:1077 / 1082
页数:6
相关论文
共 19 条
[1]   A Randomized Trial of Roxadustat in Anemia of Kidney Failure: SIERRAS Study [J].
Charytan, Chaim ;
Manllo-Karim, Roberto ;
Martin, Edouard R. ;
Steer, Dylan ;
Bernardo, Marializa ;
Dua, Sohan L. ;
Moustafa, Moustafa A. ;
Saha, Gopal ;
Bradley, Charles ;
Eyassu, Meraf ;
Leong, Robert ;
Saikali, Khalil G. ;
Liu, Cameron ;
Szczech, Lynda ;
Yu, Kin-Hung P. .
KIDNEY INTERNATIONAL REPORTS, 2021, 6 (07) :1829-1839
[2]   Nephrotoxicity Evidence in patients receiving cisplatin therapy [J].
Duffy, Elizabeth A. ;
Fitzgerald, Wendy ;
Boyle, Kelley ;
Rohatgi, Radha .
CLINICAL JOURNAL OF ONCOLOGY NURSING, 2018, 22 (02) :175-183
[3]   Tubular von Hippel-Lindau Knockout Protects against Rhabdomyolysis-Induced AKI [J].
Faehling, Michael ;
Mathia, Susanne ;
Paliege, Alexander ;
Koesters, Robert ;
Mrowka, Ralf ;
Peters, Harm ;
Persson, Pontus Boerje ;
Neumayer, Hans-Hellmut ;
Bachmann, Sebastian ;
Rosenberger, Christian .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2013, 24 (11) :1806-1819
[4]   On the Discovery, Biological Effects, and Use of Cisplatin and Metallocenes in Anticancer Chemotherapy [J].
Gomez-Ruiz, Santiago ;
Maksimovic-Ivanic, Danijela ;
Mijatovic, Sanja ;
Kaluderovic, Goran N. .
BIOINORGANIC CHEMISTRY AND APPLICATIONS, 2012, 2012
[5]   Diverse Role of TGF-β in Kidney Disease [J].
Gu, Yue-Yu ;
Liu, Xu-Sheng ;
Huang, Xiao-Ru ;
Yu, Xue-Qing ;
Lan, Hui-Yao .
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2020, 8
[6]   A Pharmacodynamic Evaluation of the Protective Effects of Roxadustat Against Hypoxic Injury at High Altitude [J].
Guo, Qianwen ;
Li, Xue ;
Li, Wenbin ;
Wang, Rong ;
Zhao, Anpeng ;
Wang, Zihan .
DRUG DESIGN DEVELOPMENT AND THERAPY, 2023, 17 :75-85
[7]   Roxadustat attenuates experimental pulmonary fibrosis in vitro and in vivo [J].
Huang, Haidi ;
Wang, Xin ;
Zhang, Xue ;
Wang, Hongbo ;
Jiang, Wanglin .
TOXICOLOGY LETTERS, 2020, 331 :112-121
[8]  
Kielkopf Clara L, 2020, Cold Spring Harb Protoc, V2020, P102269, DOI 10.1101/pdb.prot102269
[9]   Pretreatment with Roxadustat (FG-4592) Attenuates Folic Acid-Induced Kidney Injury through Antiferroptosis via Akt/GSK-3β/Nrf2 Pathway [J].
Li, Xue ;
Zou, Yu ;
Xing, Jia ;
Fu, Yuan-Yuan ;
Wang, Kai-Yue ;
Wan, Peng-Zhi ;
Zhai, Xiao-Yue .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2020, 2020
[10]   Antianemia Drug Roxadustat (FG-4592) Protects Against Doxorubicin-Induced Cardiotoxicity by Targeting Antiapoptotic and Antioxidative Pathways [J].
Long, Guangfeng ;
Chen, Hongbing ;
Wu, Mengying ;
Li, Yuanyuan ;
Gao, Ling ;
Huang, Songming ;
Zhang, Yue ;
Jia, Zhanjun ;
Xia, Weiwei .
FRONTIERS IN PHARMACOLOGY, 2020, 11