Protective Role of Hinokitiol Against H2O2-Induced Injury in Human Corneal Epithelium

Curr Eye Res. 2017 Jan;42(1):47-53. doi: 10.3109/02713683.2016.1151530. Epub 2016 Jun 7.

Abstract

Purpose: We recently found that hinokitiol has anti-inflammatory activity in human corneal epithelial (HCE) cells. Herein, we investigated the protective role of hinokitiol against H2O2-induced injury in HCE cells and the mechanisms that underlie its action.

Methods: HCE cells were incubated with different concentrations of hinokitiol or dimethylsulfoxide (DMSO), which served as a vehicle control, before H2O2 stimulus. The cell viability was evaluated using a cell counting kit-8 (CCK-8) assay. TUNEL, phosphorylated histone γH2A.X, cleaved caspase-3 expression analyses, and location of cytochrome c were conducted to detect cell injury and apoptosis. Reactive oxygen species (ROS), catalase (CAT), superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), and total antioxidative capacity (T-AOC) were used to determine oxidative stress. Bcl-2 and Bax protein expressions were measured by western blotting.

Results: Hinokitiol significantly improved the cell viability, decreased the apoptosis rate, inhibited DNA damage, and reduced cleaved caspase-3 expression and the leakage of cytochrome c from mimitochondrion to cytoplasm of HCE cells against the oxidative stress induced by H2O2. Generation of ROS and MDA and decreased activity of CAT, SOD, and T-AOC were also ameliorated by hinokitiol administration. Moreover, Bcl-2 expression was down-regulated while Bax was up-regulated by H2O2 stimulus, which were reversed by hinokitiol application.

Conclusion: Hinokitiol protects HCE cells against H2O2-induced injury likely by its antioxidant activity and modulating the Bcl-2 signaling pathway.

Keywords: Antioxidant; ROS; apoptosis; hinokitiol; human corneal epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western
  • Caspase 3 / metabolism
  • Catalase / metabolism
  • Cell Survival / drug effects*
  • Cell Survival / physiology
  • Cells, Cultured
  • Cytoprotection
  • Dimethyl Sulfoxide / pharmacology
  • Epithelium, Corneal / drug effects*
  • Epithelium, Corneal / metabolism
  • Humans
  • Hydrogen Peroxide / toxicity*
  • In Situ Nick-End Labeling
  • Monoterpenes / pharmacology*
  • Oxidants / toxicity*
  • Oxidative Stress
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism
  • Tropolone / analogs & derivatives*
  • Tropolone / pharmacology
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anti-Infective Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • BAX protein, human
  • Monoterpenes
  • Oxidants
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Tropolone
  • Hydrogen Peroxide
  • Catalase
  • Superoxide Dismutase
  • Caspase 3
  • beta-thujaplicin
  • Dimethyl Sulfoxide