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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
Peipei Li Peipei Li 1,2,3,4Duopin Li Duopin Li 1,2,3,4Yanfang Lu Yanfang Lu 1,2,3,4Shaokang Pan Shaokang Pan 1,2,3,4Fei Cheng Fei Cheng 1,2,3,4Shen Li Shen Li 5Xiaonan Zhang Xiaonan Zhang 1,2,3,4Jin-Ling Huo Jin-Ling Huo 1,2,3,4*Dongwei Liu Dongwei Liu 1,2,3,4*Zhangsuo Liu Zhangsuo Liu 1,2,3,4*
  • 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

The final, formatted version of the article will be published soon.

    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

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.