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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1457230
This article is part of the Research Topic Crosstalk in Ferroptosis, Immunity & Inflammation View all 7 articles
GSTT1/GSTM1 deficiency aggravated cisplatin-induced acute kidney injury via ROS-triggered ferroptosis
Provisionally accepted- 1 Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- 2 Research Institute of Nephrology, Zhengzhou University, Zhengzhou, Henan Province, China
- 3 Henan Province Research Center For Kidney Disease, Zhengzhou, China
- 4 Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, China
- 5 Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
Cisplatin is a widely used chemotherapeutic agent prescribed to treat solid tumors. However, its clinical application is limited because of cisplatin-induced nephrotoxicity. A known complication of cisplatin is acute kidney injury (AKI).Deletion polymorphisms of GSTM1 and GSTT1, members of the glutathione Stransferase family, are common in humans and are presumed to be associated with various kidney diseases. However, the specific roles and mechanisms of GSTM1 and GSTT1 in cisplatin induced AKI remain unclear. Here, we found that GSTT1 and GSTM1 were downregulated in the renal tubular cells of AKI patients and cisplatintreated mice. Compared with WT mice, Gstm1/Gstt1-DKO mice were phenotypically normal but developed more severe kidney dysfunction and exhibited increased ROS levels and severe ferroptosis after injecting cisplatin. Thus, our study revealed that GSTM1 and GSTT1 can protect renal tubular cells against cisplatin-induced nephrotoxicity and ferroptosis, and genetic screening for GSTM1 and GSTT1 polymorphisms can help determine a standard cisplatin dose for cancer patients undergoing chemotherapy.
Keywords: AKI, Cisplatin, GSTT1, GSTM1, ROS, ferroptosis
Received: 30 Jun 2024; Accepted: 23 Aug 2024.
Copyright: © 2024 Li, Li, Lu, Pan, Cheng, Li, Zhang, Huo, Liu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jin-Ling Huo, Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
Dongwei Liu, Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
Zhangsuo Liu, Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
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