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Article Open Access

Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway

  • Authors:
    • Yan Hao
    • Jie Miao
    • Wenjia Liu
    • Li Peng
    • Yue Chen
    • Qing Zhong
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, Zigong First People's Hospital, Zigong, Sichuan 643000, P.R. China, Department of Imaging Medicine, Sichuan Vocational College of Health and Rehabilitation, Zigong, Sichuan 643000, P.R. China
    Copyright: © Hao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 511-522
    |
    Published online on: December 1, 2020
       https://doi.org/10.3892/ijmm.2020.4805
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Abstract

Acute kidney injury (AKI) is characterized by an abrupt deterioration of renal function. Formononetin (FOR) protects against cisplatin (CIS)‑induced AKI, and it has various potential pharmacological and biological effects, including anti‑inflammatory, antioxidative and anti‑apoptotic effects. The current study investigated the role of FOR in CIS‑induced AKI. Rats were treated with CIS to establish an AKI model, followed by treatment with FOR. HK‑2 cells were treated with CIS, FOR, GW6471 [a peroxisome proliferator‑activated receptor α (PPARα) antagonist], eupatilin (a PPARα agonist) and nuclear factor erythroid 2‑related factor 2 (Nrf2) small interfering RNA (siNrf2), and cell proliferation and apoptosis were determined by MTT and flow cytometry assays. The mRNA and proteins levels of PPARα, Nrf2, heme oxygenase‑1 (HO‑1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were measured by reverse transcription‑quantitative PCR and western blotting. The results demonstrated that FOR attenuated the histopathological changes, the levels of blood urea nitrogen, creatinine, TNF‑α and IL‑1β, and the MDA content and MPO activity, whereas it enhanced CAT activity in the AKI rat model. Furthermore, FOR and eupatilin promoted cell viability and CAT activity, and increased the levels of PPARα, Nrf2 and HO‑1 and NQO1, but suppressed apoptosis and MPO activity, and reduced the levels of MDA, TNF‑α and IL‑1β in CIS‑treated HK‑2 cells. Notably, the aforementioned effects were reversed by GW6471 treatment or siNrf2 transfection. In conclusion, FOR protects against CIS‑induced AKI via activation of the PPARα/Nrf2/HO‑1/NQO1 pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Hao Y, Miao J, Liu W, Peng L, Chen Y and Zhong Q: Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway. Int J Mol Med 47: 511-522, 2021.
APA
Hao, Y., Miao, J., Liu, W., Peng, L., Chen, Y., & Zhong, Q. (2021). Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway. International Journal of Molecular Medicine, 47, 511-522. https://doi.org/10.3892/ijmm.2020.4805
MLA
Hao, Y., Miao, J., Liu, W., Peng, L., Chen, Y., Zhong, Q."Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway". International Journal of Molecular Medicine 47.2 (2021): 511-522.
Chicago
Hao, Y., Miao, J., Liu, W., Peng, L., Chen, Y., Zhong, Q."Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway". International Journal of Molecular Medicine 47, no. 2 (2021): 511-522. https://doi.org/10.3892/ijmm.2020.4805
Copy and paste a formatted citation
x
Spandidos Publications style
Hao Y, Miao J, Liu W, Peng L, Chen Y and Zhong Q: Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway. Int J Mol Med 47: 511-522, 2021.
APA
Hao, Y., Miao, J., Liu, W., Peng, L., Chen, Y., & Zhong, Q. (2021). Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway. International Journal of Molecular Medicine, 47, 511-522. https://doi.org/10.3892/ijmm.2020.4805
MLA
Hao, Y., Miao, J., Liu, W., Peng, L., Chen, Y., Zhong, Q."Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway". International Journal of Molecular Medicine 47.2 (2021): 511-522.
Chicago
Hao, Y., Miao, J., Liu, W., Peng, L., Chen, Y., Zhong, Q."Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway". International Journal of Molecular Medicine 47, no. 2 (2021): 511-522. https://doi.org/10.3892/ijmm.2020.4805
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