Perillyl alcohol protects human renal tubular epithelial cells from hypoxia/reoxygenation injury via inhibition of ROS, endoplasmic reticulum stress and activation of PI3K/Akt/eNOS pathway

Biomed Pharmacother. 2017 Nov:95:662-669. doi: 10.1016/j.biopha.2017.08.129. Epub 2017 Sep 7.

Abstract

Ischemia/reperfusion (I/R) injury plays an essential role in renal transplantation, and represents a crucial risk factor for allograft dysfunction and acute renal failure. Modulation of oxidative stress is an effective therapeutic strategy for I/R injury. Perillyl alcohol (POH), a dietary monoterpene with antioxidant activity is found in a variety of plants. The study was carried out to investigate whether treatment of POH could reduce hypoxia/reoxygenation (H/R)-induced injury. H/R induced significant injury in HK-2 cells. H/R caused an increase in ROS level, apoptosis and ER stress. Meanwhile H/R also inhibited the cell viability and PI3K/Akt/eNOS signaling pathway. Pretreatment with POH prior to H/R improved cell viability, reduce ROS level, ER stress and apoptosis. Moreover, POH could also activate the PI3K/Akt/eNOS pathway. Therefore, POH may possess protective effects in H/R-induced cellular damage.

Keywords: Apoptosis; ER stress; Hypoxia/reoxygenation (H/R) injury; PI3K/Akt/eNOS pathway; Perillyl alcohol; ROS.

MeSH terms

  • Apoptosis / drug effects
  • Cell Hypoxia / drug effects
  • Cell Line
  • Cytoprotection / drug effects
  • Endoplasmic Reticulum Stress / drug effects*
  • Enzyme Activation / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology*
  • Humans
  • Kidney Tubules / pathology*
  • Monoterpenes / pharmacology*
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress / drug effects
  • Oxygen / toxicity*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protective Agents / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Monoterpenes
  • Protective Agents
  • Reactive Oxygen Species
  • perillyl alcohol
  • Nitric Oxide Synthase Type III
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Oxygen