Characterization of hydrogen sulfide toxicity to human corneal stromal fibroblasts

Ann N Y Acad Sci. 2020 Nov;1480(1):207-218. doi: 10.1111/nyas.14498. Epub 2020 Sep 20.

Abstract

Hydrogen sulfide gas (H2 S) is a chemical weapon and a common environmental pollutant. H2 S intoxication is lethal to humans and animals. H2 S contact to the eye can cause vision loss. However, the molecular mechanisms associated with H2 S toxicity to the cornea remain unclear, and no specific therapy exists to mitigate ocular damage from H2 S. Here, we report H2 S-induced cytotoxicity and the parameters contributing to the molecular mechanisms associated with corneal toxicity using primary human corneal stromal fibroblasts (hCSFs) in vitro. Sodium hydrosulfide (NaSH) was used as a source of H2 S, and the cytotoxicity of H2 S was determined by treating hCSF cells with varying concentrations of NaSH (0-10 mM) for 0-72 hours. Changes in cell proliferation, oxidative stress factors, and the expression of inflammatory and fibrotic genes were studied using standard commercial kits and qRT-PCR. NaSH exposure to hCSFs showed dose- and time-dependent cytotoxicity. The IC50 of NaSH was determined to be 5.35 mM. NaSH 5.35 mM exposure led to significantly decreased cytochrome c oxidase activity, increased ROS production, and increased expression of inflammatory and fibrotic genes in hCSF cells. H2 S/NaSH exposure alters normal mitochondrial function, oxidative stress, and inflammatory and fibrotic gene responses in corneal stromal fibroblasts in vitro.

Keywords: cornea; corneal toxicity; fibroblasts; hydrogen sulfide; inflammation; oxidative stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cells, Cultured
  • Corneal Stroma / metabolism*
  • Corneal Stroma / pathology
  • Cytotoxins / toxicity*
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gene Expression Regulation / drug effects*
  • Humans
  • Hydrogen Sulfide / toxicity*
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism

Substances

  • Cytotoxins
  • Reactive Oxygen Species
  • Hydrogen Sulfide