A polysaccharide from Huaier ameliorates cisplatin nephrotoxicity by decreasing oxidative stress and apoptosis via PI3K/AKT signaling

Int J Biol Macromol. 2019 Oct 15:139:932-943. doi: 10.1016/j.ijbiomac.2019.07.219. Epub 2019 Aug 1.

Abstract

Cisplatin (CP), a common chemotherapy drug used in treatment of malignant tumors. Due to various side effects such as nephrotoxicity (kidney damage), it's efficiency and therapeutic application are limited. This study focuses on finding a suitable drug that would attenuate the side effects like kidney damage, caused by CP. Huaier polysaccharide (HP-1), an extraction of Trametes robiniophila Murr, with a molecular weight of 3 × 104 Da. Previous studies have shown that HP-1, exhibits anti-tumor potential and immunomodulatory effects. We hypothesized that HP-1 has the effect of attenuating the nephrotoxicity caused by CP chemotherapy and protecting renal function. Through our experiments, we observed that HP-1 can attenuate the level of oxidative stress, inflammation and mitochondrial dysfunction, thereby reducing kidney damage. In vitro, we observed that HP-1 significantly inhibits CP-induced renal tubular cell apoptosis and cell cycle arrest. In addition, HP-1 also affects the expression level of the protein by regulating the PI3K/Akt/mTOR signaling pathway and thus attenuates the side effects induced by cisplatin. Therefore, HP-1 may be a potential drug for preventing CP-induced renal damage.

Keywords: Cisplatin; Huaier polysaccharide (HP-1); Kidney damage.

MeSH terms

  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Cell Line, Tumor
  • Cisplatin / adverse effects*
  • Complex Mixtures / chemistry*
  • Humans
  • Kidney / cytology*
  • Kidney / drug effects
  • Mitochondria / drug effects
  • Mitochondria / pathology
  • Oxidative Stress / drug effects*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Polysaccharides / chemistry
  • Polysaccharides / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism
  • Trametes / chemistry*

Substances

  • Complex Mixtures
  • Polysaccharides
  • huaier
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Cisplatin