4.7 Article

Wedelolactone alleviates doxorubicin-induced inflammation and oxidative stress damage of podocytes by IκK/IκB/NF-κB pathway

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 117, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2019.109088

Keywords

Wedelolactone; Doxorubicin; Podocyte; Inflammation; Oxidative stress

Funding

  1. National Natural Science Foundation Committee of P.R. China [81603382, 81703775]
  2. Jiangsu province high-level health personnel Six-One Project [LGY2017085]
  3. Jiangsu Province Youth Medical Key Talent Project [QNRC2016634]
  4. Innovative Research Team of Health Development Project with Science and Education in Jiangsu Province [CXTDB2017003]
  5. Program for Innovative Research Team of Six Talent Peaks Project in Jiangsu Province [SWYY-CXTD-004]
  6. Jiangsu Postdoctoral Fund [1601023C]
  7. China Postdoctoral Fund [2016M601864]
  8. Double First-Class University project of China Pharmaceutical University [CPU2018GF07, CPU2018PZQ19]
  9. key special items of research on modernization of traditional Chinese medicine [2018YFC1706900]

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The acute kidney injury(AKI) caused by nephrotoxic drugs contributes to inflammation and oxidative injury in podocytes. Wedelolactone (WED), a natural compound, is found with activities as anti-inflammation, anti-oxidative, anti-free radical, and etc. In this present study, MPC-5 cells were exposed to the nephrotoxic drugs doxorubicin (DOX). The results showed that WED significantly increased the SOD activity, CAT and GSH-Px levels, while significantly decreased the MDA content and ROS levels in DOX-induced MPC-5 cells. WED could also significantly decrease the levels of cytokines IL-6, MCP-1, TNF-alpha, and TGF-beta 1. Additionally, the activation and phosphorylation of I kappa Ka, I kappa Ba and NF-kappa B p65 was inhibited by WED. The co-treatment of PDTC (NF-kappa B inhibitor) and WED significantly reduced NF-kappa B p65 phosphorylation. These findings suggested that WED alleviated inflammation and oxidative stress of doxorubicin-induced MPC-5 cells through I kappa K/I kappa B/NF-kappa B signaling pathway.

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