Open Access

Effects and molecular mechanism of pachymic acid on ferroptosis in renal ischemia reperfusion injury

  • Authors:
    • Gui-Ping Jiang
    • Yue-Juan Liao
    • Li-Li Huang
    • Xu-Jia Zeng
    • Xiao-Hui Liao
  • View Affiliations

  • Published online on: November 19, 2020     https://doi.org/10.3892/mmr.2020.11704
  • Article Number: 63
  • Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute kidney injury (AKI) is a common clinical disease. Ferropotosis, a new type of regulatory cell death, serves an important regulatory role in AKI. Pachymic acid (PA), a lanostane‑type triterpenoid from Poria cocos, has been reported to be protective against AKI. However, the protective mechanism of PA in AKI is not yet fully understood. The present study aimed to investigate the effect and molecular mechanism of PA on ferroptosis in renal ischemia reperfusion injury in vivo. A total of 30 mice were intraperitoneally injected with 5, 10 and 20 mg/kg PA for 3 days. A bilateral renal pedicle clip was used for 40 min to induce renal ischemia‑reperfusion injury and establish the model. The results demonstrated that treatment with PA decreased serum creatinine and blood urea nitrogen, and ameliorated renal pathological damage. Transmission electron microscopy revealed no characteristic changes in ferroptosis in the mitochondria of the renal tissue in the high‑dose PA group, and only mild edema. Furthermore, treatment with PA increased glutathione expression, and decreased the expression levels of malondialdehyde and cyclooxygenase 2. Treatment with PA enhanced the protein and mRNA expression levels of the ferroptosis related proteins, glutathione peroxidase 4 (GPX4), solute carrier family 7 (cationic amino acid transporter, y+ system) member 11 (SLC7A11) and heme oxygenase 1 (HO‑1) in the kidney, and increased the expression levels of nuclear factor erythroid derived 2 like 2 (NRF2) signaling pathway members. Taken together, the results of the present study suggest that PA has a protective effect on ischemia‑reperfusion induced acute kidney injury in mice, which may be associated with the inhibition of ferroptosis in the kidneys through direct or indirect activation of NRF2, and upregulation of the expression of the downstream ferroptosis related proteins, GPX4, SLC7A11 and HO‑1.
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January-2021
Volume 23 Issue 1

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Spandidos Publications style
Jiang G, Liao Y, Huang L, Zeng X and Liao X: Effects and molecular mechanism of pachymic acid on ferroptosis in renal ischemia reperfusion injury. Mol Med Rep 23: 63, 2021
APA
Jiang, G., Liao, Y., Huang, L., Zeng, X., & Liao, X. (2021). Effects and molecular mechanism of pachymic acid on ferroptosis in renal ischemia reperfusion injury. Molecular Medicine Reports, 23, 63. https://doi.org/10.3892/mmr.2020.11704
MLA
Jiang, G., Liao, Y., Huang, L., Zeng, X., Liao, X."Effects and molecular mechanism of pachymic acid on ferroptosis in renal ischemia reperfusion injury". Molecular Medicine Reports 23.1 (2021): 63.
Chicago
Jiang, G., Liao, Y., Huang, L., Zeng, X., Liao, X."Effects and molecular mechanism of pachymic acid on ferroptosis in renal ischemia reperfusion injury". Molecular Medicine Reports 23, no. 1 (2021): 63. https://doi.org/10.3892/mmr.2020.11704