Astragalosides IV protected the renal tubular epithelial cells from free fatty acids-induced injury by reducing oxidative stress and apoptosis

Biomed Pharmacother. 2018 Dec:108:679-686. doi: 10.1016/j.biopha.2018.09.049. Epub 2018 Sep 21.

Abstract

Renal tubular injury is associated with the development of diabetic nephropathy (DN) and the end-stage renal disease (ESRD). Free fatty acids (FFAs)-associated lipotoxicity contributes to injury of proximal renal tubular epithelial (HK-2) cells in diabetes. Palmitic acid (PA) which is the most abundant saturated fatty acid in FFAs is closely associated with the gradual decline of renal function. Astragalosides IV (AS-IV) has a variety of pharmacological effects such as anti-inflammation and anti-oxidation. In the current study, we investigated the effects of AS-IV on PA-induced apoptosis of HK-2 cells and the underlying mechanisms. The results showed that AS-IV (10, 20, 40 μmol/L) could alleviate PA-induced apoptosis of HK-2 cells. We found that AS-IV reduced the expression of Bax and cleaved-caspase3, but increased the expression of Bcl-2 and phosphorylated Nrf2 in HK-2 cells. Moreover, AS-IV reduced the level of reactive oxygen species (ROS) in the cells. Our study suggests that AS-IV could protect against PA-induced apoptosis in HK-2 cells by inhibiting ROS generation and apoptotic protein expression. This study may provide a new theoretical option for the patients with type 2 diabetes.

Keywords: Apoptosis; Astragaloside IV; Human renal tubular epithelial cells; Reactive oxygen species.

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Fatty Acids, Nonesterified / pharmacology*
  • Glucose / metabolism
  • Humans
  • Kidney Tubules / drug effects*
  • Kidney Tubules / metabolism
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects*
  • Protective Agents / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Saponins / pharmacology*
  • Signal Transduction / drug effects
  • Triterpenes / pharmacology*

Substances

  • Fatty Acids, Nonesterified
  • Protective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Saponins
  • Triterpenes
  • astragaloside A
  • Caspase 3
  • Glucose