1. Academic Validation
  2. Mitochondria-derived reactive oxygen species are involved in renal cell ferroptosis during lipopolysaccharide-induced acute kidney injury

Mitochondria-derived reactive oxygen species are involved in renal cell ferroptosis during lipopolysaccharide-induced acute kidney injury

  • Int Immunopharmacol. 2022 Jun;107:108687. doi: 10.1016/j.intimp.2022.108687.
Nan-Nan Liang 1 Ying Zhao 1 Yue-Yue Guo 1 Zhi-Hui Zhang 2 Lan Gao 1 De-Xin Yu 2 De-Xiang Xu 3 Shen Xu 4
Affiliations

Affiliations

  • 1 Department of Toxicology, Anhui Medical University, Hefei, China.
  • 2 The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
  • 3 Department of Toxicology, Anhui Medical University, Hefei, China. Electronic address: [email protected].
  • 4 The Second Affiliated Hospital, Anhui Medical University, Hefei, China. Electronic address: [email protected].
Abstract

Our earlier studies indicated that Reactive Oxygen Species (ROS) were involved in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). The present study aimed to explore the role of mitochondria-derived ROS on renal cell Ferroptosis during LPS-induced AKI. Male CD-1 mice were intraperitoneally injected with LPS (2.0 mg/kg). Renal MDA and 4HNE residue, two markers of lipid peroxidation, were increased in LPS-exposed mice. Oxidized lipids were detected in LPS-treated human HK-2 cells. In vivo, ferroptosis-characteristic ultrastructure changes, including cell volume reduction, nuclear pyknosis and smaller mitochondria, were shown in renal cortex. In vitro, abnormal alteration of mitochondrial membrane potential was observed in LPS-treated human HK-2 cells. Ferrostatin-1, a specific inhibitor of Ferroptosis, attenuated LPS-evoked renal lipid peroxidation, ferroptosis-characteristic mitochondrial damage and renal cell death. Mechanistically, mitochondria-derived ROS were elevated in LPS-stimulated HK-2 cells. MitoQ, a mitochondria-targeted antioxidant, almost completely scavenged LPS-stimulated mitochondrial ROS in human HK-2 cells. Moreover, pretreatment with MitoQ attenuated LPS-induced GSH depletion and lipid peroxidation in mouse kidney. Finally, pretreatment with MitoQ alleviated LPS-induced renal cell death and AKI. Taken together, these results suggest that mitochondria-derived ROS contribute, at least partially, to renal cell Ferroptosis during LPS-induced AKI. Mitochondria-targeted antioxidants may be potential therapeutic agents for sepsis-induced AKI.

Keywords

Acute kidney injury; Ferroptosis; Mitochondria-derived reactive oxygen species; Mitochondria-targeted antioxidants.

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Products
  • Cat. No.
    Product Name
    Description
    Target
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  • HY-100579
    99.96%, Ferroptosis Inhibitor