Ultra-sensitive analysis of exhaled biomarkers in ozone-exposed mice via PAI-TOFMS assisted with machine learning algorithms

J Hazard Mater. 2024 May 15:470:134151. doi: 10.1016/j.jhazmat.2024.134151. Epub 2024 Mar 27.

Abstract

Ground-level ozone ranks sixth among common air pollutants. It worsens lung diseases like asthma, emphysema, and chronic bronchitis. Despite recent attention from researchers, the link between exhaled breath and ozone-induced injury remains poorly understood. This study aimed to identify novel exhaled biomarkers in ozone-exposed mice using ultra-sensitive photoinduced associative ionization time-of-flight mass spectrometry and machine learning. Distinct ion peaks for acetonitrile (m/z 42, 60, and 78), butyronitrile (m/z 70, 88, and 106), and hydrogen sulfide (m/z 35) were detected. Integration of tissue characteristics, oxidative stress-related mRNA expression, and exhaled breath condensate free-radical analysis enabled a comprehensive exploration of the relationship between ozone-induced biological responses and potential biomarkers. Under similar exposure levels, C57BL/6 mice exhibited pulmonary injury characterized by significant inflammation, oxidative stress, and cardiac damage. Notably, C57BL/6 mice showed free radical signals, indicating a distinct susceptibility profile. Immunodeficient non-obese diabetic Prkdc-/-/Il2rg-/- (NPI) mice exhibited minimal biological responses to pulmonary injury, with little impact on the heart. These findings suggest a divergence in ozone-induced damage pathways in the two mouse types, leading to alterations in exhaled biomarkers. Integrating biomarker discovery with comprehensive biopathological analysis forms a robust foundation for targeted interventions to manage health risks posed by ozone exposure.

Keywords: Exhaled biomarker; Immunodeficiency; Machine learning; Mass spectrometry; Ozone-induced damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants / analysis
  • Air Pollutants / toxicity
  • Animals
  • Biomarkers* / analysis
  • Biomarkers* / metabolism
  • Breath Tests*
  • Exhalation
  • Lung Injury / chemically induced
  • Lung Injury / metabolism
  • Machine Learning*
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL*
  • Oxidative Stress / drug effects
  • Ozone* / toxicity

Substances

  • Ozone
  • Biomarkers
  • Air Pollutants