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Article Open Access

Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation

  • Authors:
    • Dal Kim
    • Woong Park
    • Sik Lee
    • Won Kim
    • Sung Kwang Park
    • Kyung Pyo Kang
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Jeollabuk‑do 54907, Republic of Korea
    Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3665-3672
    |
    Published online on: August 3, 2018
       https://doi.org/10.3892/mmr.2018.9350
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Abstract

Cisplatin‑based chemotherapy is commonly used in the treatment of solid tumors; however, this agent is limited by its adverse effects on normal tissues, including the kidneys, ears and peripheral nerves. Mechanisms of cisplatin nephrotoxicity are proposed to involve oxidative stress, inflammation, cellular apoptosis and cell cycle regulation. Sirtuin 3 (Sirt3) is a member of the sirtuin family of NAD+‑dependent enzymes with homology to Saccharomyces cerevisiae gene silent information regulator 2. Sirt3 is located in mitochondria and is involved in mitochondrial energy metabolism and function; however, the role of Sirt3 in cisplatin nephrotoxicity remains unclear. In the present study, whether Sirt3 has anti‑inflammatory and anti‑apoptotic effects on cisplatin‑induced nephrotoxicity was investigated in mice. Sirt3 knockout mice (Sirt3(‑/‑)) and corresponding wild type mice were employed in the present study. Cisplatin nephrotoxicity was induced by intraperitoneal injection of cisplatin (20 mg/kg). After 3 days following cisplatin treatment, blood and kidney tissues were harvested. Renal function and histology were evaluated. Tubular apoptosis, cell adhesion molecule expression, and inflammatory cells were evaluated by immunohistochemistry and western blot analysis. Following the induction of cisplatin nephrotoxicity, renal function was significantly aggravated in Sirt3 knockout (KO) mice. Tubular injury and inflammatory cell infiltration were significantly increased in Sirt3KO mice compared with wild type mice. Terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end label‑positive tubular cells and renal monocyte chemoattractant protein‑1 expression levels were increased in Sirt3KO mice compared with in wild type mice. In summary, the absence of Sirt3 aggravated in renal injury by increasing renal inflammation and tubular apoptosis. The results of the present study suggested that Sirt3 may have an important role in cisplatin‑induced nephrotoxicity.
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Copy and paste a formatted citation
Spandidos Publications style
Kim D, Park W, Lee S, Kim W, Park SK and Kang KP: Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation. Mol Med Rep 18: 3665-3672, 2018.
APA
Kim, D., Park, W., Lee, S., Kim, W., Park, S.K., & Kang, K.P. (2018). Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation. Molecular Medicine Reports, 18, 3665-3672. https://doi.org/10.3892/mmr.2018.9350
MLA
Kim, D., Park, W., Lee, S., Kim, W., Park, S. K., Kang, K. P."Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation". Molecular Medicine Reports 18.4 (2018): 3665-3672.
Chicago
Kim, D., Park, W., Lee, S., Kim, W., Park, S. K., Kang, K. P."Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation". Molecular Medicine Reports 18, no. 4 (2018): 3665-3672. https://doi.org/10.3892/mmr.2018.9350
Copy and paste a formatted citation
x
Spandidos Publications style
Kim D, Park W, Lee S, Kim W, Park SK and Kang KP: Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation. Mol Med Rep 18: 3665-3672, 2018.
APA
Kim, D., Park, W., Lee, S., Kim, W., Park, S.K., & Kang, K.P. (2018). Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation. Molecular Medicine Reports, 18, 3665-3672. https://doi.org/10.3892/mmr.2018.9350
MLA
Kim, D., Park, W., Lee, S., Kim, W., Park, S. K., Kang, K. P."Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation". Molecular Medicine Reports 18.4 (2018): 3665-3672.
Chicago
Kim, D., Park, W., Lee, S., Kim, W., Park, S. K., Kang, K. P."Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation". Molecular Medicine Reports 18, no. 4 (2018): 3665-3672. https://doi.org/10.3892/mmr.2018.9350
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