Airborne Exposure of the Cornea to PM10 Induces Oxidative Stress and Disrupts Nrf2 Mediated Anti-Oxidant Defenses

Int J Mol Sci. 2023 Feb 15;24(4):3911. doi: 10.3390/ijms24043911.

Abstract

The purpose of this study is to test the effects of whole-body animal exposure to airborne particulate matter (PM) with an aerodynamic diameter of <10 μm (PM10) in the mouse cornea and in vitro. C57BL/6 mice were exposed to control or 500 µg/m3 PM10 for 2 weeks. In vivo, reduced glutathione (GSH) and malondialdehyde (MDA) were analyzed. RT-PCR and ELISA evaluated levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and inflammatory markers. SKQ1, a novel mitochondrial antioxidant, was applied topically and GSH, MDA and Nrf2 levels were tested. In vitro, cells were treated with PM10 ± SKQ1 and cell viability, MDA, mitochondrial ROS, ATP and Nrf2 protein were tested. In vivo, PM10 vs. control exposure significantly reduced GSH, corneal thickness and increased MDA levels. PM10-exposed corneas showed significantly higher mRNA levels for downstream targets, pro-inflammatory molecules and reduced Nrf2 protein. In PM10-exposed corneas, SKQ1 restored GSH and Nrf2 levels and lowered MDA. In vitro, PM10 reduced cell viability, Nrf2 protein, and ATP, and increased MDA, and mitochondrial ROS; while SKQ1 reversed these effects. Whole-body PM10 exposure triggers oxidative stress, disrupting the Nrf2 pathway. SKQ1 reverses these deleterious effects in vivo and in vitro, suggesting applicability to humans.

Keywords: Nrf2; SKQ1; cornea; mouse; particulate matter.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Antioxidants* / pharmacology
  • Cornea* / drug effects
  • Cornea* / metabolism
  • Environmental Exposure*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress* / drug effects
  • Particulate Matter* / antagonists & inhibitors
  • Particulate Matter* / toxicity
  • Plastoquinone* / pharmacology
  • Reactive Oxygen Species / metabolism

Substances

  • Adenosine Triphosphate
  • Antioxidants
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Particulate Matter
  • 10-(6'-plastoquinonyl)decyltriphenylphosphonium
  • Plastoquinone