Evaluation of urinary limonene metabolites as biomarkers of exposure to greenness

Zhengzhi Xie; Saurin R Sutaria; Jin Y Chen; Hong Gao; Daniel J Conklin; Rachel J Keith; Sanjay Srivastava; Pawel Lorkiewicz; Aruni Bhatnagar

doi:10.1016/j.envres.2023.117991

Evaluation of urinary limonene metabolites as biomarkers of exposure to greenness

Environ Res. 2024 Mar 15:245:117991. doi: 10.1016/j.envres.2023.117991. Epub 2023 Dec 22.

Authors

Zhengzhi Xie¹, Saurin R Sutaria², Jin Y Chen³, Hong Gao⁴, Daniel J Conklin⁵, Rachel J Keith⁶, Sanjay Srivastava⁷, Pawel Lorkiewicz⁸, Aruni Bhatnagar⁹

Affiliations

¹ Christina Lee Brown Envirome Institute, University of Louisville, USA; Superfund Research Center, University of Louisville, USA; American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, USA; Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, 40202, USA. Electronic address: zhengzhi.xie@louisville.edu.
² Christina Lee Brown Envirome Institute, University of Louisville, USA; Superfund Research Center, University of Louisville, USA; American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, USA; Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, 40202, USA. Electronic address: saurin.sutaria@louisville.edu.
³ Christina Lee Brown Envirome Institute, University of Louisville, USA; Superfund Research Center, University of Louisville, USA; American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, USA; Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, 40202, USA. Electronic address: jin.chen@louisville.edu.
⁴ Christina Lee Brown Envirome Institute, University of Louisville, USA; Superfund Research Center, University of Louisville, USA; American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, USA; Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, 40202, USA. Electronic address: hong.gao@louisville.edu.
⁵ Christina Lee Brown Envirome Institute, University of Louisville, USA; Superfund Research Center, University of Louisville, USA; American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, USA; Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, 40202, USA. Electronic address: dj.conklin@louisville.edu.
⁶ Christina Lee Brown Envirome Institute, University of Louisville, USA; Superfund Research Center, University of Louisville, USA; American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, USA; Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, 40202, USA. Electronic address: rachel.keith@louisville.edu.
⁷ Christina Lee Brown Envirome Institute, University of Louisville, USA; Superfund Research Center, University of Louisville, USA; American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, USA; Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, 40202, USA. Electronic address: sanjay.srivastava@louisville.edu.
⁸ Christina Lee Brown Envirome Institute, University of Louisville, USA; Superfund Research Center, University of Louisville, USA; American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, USA; Department of Chemistry, University of Louisville, USA; Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, 40202, USA. Electronic address: pawel.lorkiewicz@louisville.edu.
⁹ Christina Lee Brown Envirome Institute, University of Louisville, USA; Superfund Research Center, University of Louisville, USA; American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, USA; Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, 40202, USA. Electronic address: aruni.bhatnagar@louisville.edu.

PMID: 38141921
PMCID: PMC10922478 (available on 2025-03-15)
DOI: 10.1016/j.envres.2023.117991

Abstract

Exposure to plants is known to improve physical and mental health and living in areas of high vegetation is associated with better health. The addition of quantitative measures of greenness exposure at individual-level to other objective and subjective study measures will help establish cause-and-effect relationships between greenspaces and human health. Because limonene is one of the most abundant biogenic volatile organic compounds emitted by plants, we hypothesized that urinary metabolites of inhaled limonene can serve as biomarkers of exposure to greenness. To test our hypothesis, we analyzed urine samples collected from eight human volunteers after limonene inhalation or after greenness exposure using liquid chromatography-high resolution mass spectrometry-based profiling. Eighteen isomers of nine metabolites were detected in urine after limonene inhalation, and their kinetic parameters were estimated using nonlinear mixed effect models. Urinary levels of most abundant limonene metabolites were elevated after brief exposure to a forested area, and the ratio of urinary limonene metabolites provided evidence of recent exposure. The identities and structures of these metabolites were validated using stable isotope tracing and tandem mass spectral comparison. Together, these data suggest that urinary metabolites of limonene, especially uroterpenol glucuronide and dihydroperillic acid glucuronide, could be used as individualized biomarkers of greenness exposure.

Keywords: Biogenic volatile organic compounds (BVOC); Biomarker; Data-independent acquisition (DIA); Greenness exposure; LC-MS; Limonene.

MeSH terms

Biomarkers / urine
Glucuronides* / urine
Humans
Limonene
Liquid Chromatography-Mass Spectrometry
Plants*

Substances

Limonene
Glucuronides
Biomarkers

Abstract

MeSH terms

Substances

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