A rabbit model for assessment of volatile metabolite changes observed from skin: A pressure ulcer case study

Michael Schivo, Alexander A. Aksenov, Alberto Pasamontes, Raquel Cumeras, Sandra Weisker, Anita M. Oberbauer, Cristina E Davis

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Human skin presents a large, easily accessible matrix that is potentially useful for diagnostic applications based on whole body metabolite changes - some of which will be volatile and detected using minimally invasive tools. Unfortunately, identifying skin biomarkers that can be reliably linked to a particular condition is challenging due to a large variability of genetics, dietary intake, and environmental exposures within human populations. This leads to a paucity of clinically validated volatile skin biomarker compounds. Animal models present a very convenient and attractive way to circumvent many of the variability issues. The rabbit (Leporidae) is a potentially logistically useful model to study the skin metabolome, but very limited knowledge of its skin metabolites exists. Here we present the first comprehensive assessment of the volatile fraction of rabbit skin metabolites using polydimethylsiloxane sorbent patch sampling in conjunction with gas chromatography/mass spectrometry. A collection of compounds that are secreted from rabbit skin was documented, and predominantly acyclic long-chain alkyls and alcohols were detected. We then utilized this animal model to study differences between intact skin and skin with early pressure ulcers, as the latter are a major problem in intensive care units. Four New Zealand female white rabbits underwent ulcer formation on one ear with the other ear as a control. Early-stage ulcers were created with neodymium magnets. Histologic analysis showed acute heterophilic dermatitis, edema, and micro-hemorrhage on the ulcerated ears with normal findings on the control ears. The metabolomic analysis revealed subtle but noticeable differences, with several compounds associated with the oxidative stress-related degradation of lipids found to be present in greater abundances in ulcerated ears. The metabolomic findings correlate with histologic evidence of early-stage ulcers. We postulate that the Leporidae model recapitulated the vascular changes associated with ulcer formation. This study illustrates the potential usefulness of the Leporidae model for skin metabolome studies. Additionally, skin metabolome analysis may enhance an understanding of non-skin sources such as urine or breath.

Original languageEnglish (US)
Article number016007
JournalJournal of Breath Research
Volume11
Issue number1
DOIs
StatePublished - Mar 1 2017

Fingerprint

Pressure Ulcer
Rabbits
Skin
Lagomorpha
Ear
Ulcer
Metabolome
Metabolomics
Animal Models
Biomarkers
Neodymium
Magnets
Environmental Exposure
Dermatitis
Gas Chromatography-Mass Spectrometry
Blood Vessels
Intensive Care Units
Edema
Oxidative Stress
Alcohols

Keywords

  • gas chromatography/mass spectrometry (GC/MS)
  • Leporidae
  • pressure ulcers
  • skin
  • volatile organic compounds (VOCs)

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

A rabbit model for assessment of volatile metabolite changes observed from skin : A pressure ulcer case study. / Schivo, Michael; Aksenov, Alexander A.; Pasamontes, Alberto; Cumeras, Raquel; Weisker, Sandra; Oberbauer, Anita M.; Davis, Cristina E.

In: Journal of Breath Research, Vol. 11, No. 1, 016007, 01.03.2017.

Research output: Contribution to journalArticle

Schivo, Michael ; Aksenov, Alexander A. ; Pasamontes, Alberto ; Cumeras, Raquel ; Weisker, Sandra ; Oberbauer, Anita M. ; Davis, Cristina E. / A rabbit model for assessment of volatile metabolite changes observed from skin : A pressure ulcer case study. In: Journal of Breath Research. 2017 ; Vol. 11, No. 1.
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abstract = "Human skin presents a large, easily accessible matrix that is potentially useful for diagnostic applications based on whole body metabolite changes - some of which will be volatile and detected using minimally invasive tools. Unfortunately, identifying skin biomarkers that can be reliably linked to a particular condition is challenging due to a large variability of genetics, dietary intake, and environmental exposures within human populations. This leads to a paucity of clinically validated volatile skin biomarker compounds. Animal models present a very convenient and attractive way to circumvent many of the variability issues. The rabbit (Leporidae) is a potentially logistically useful model to study the skin metabolome, but very limited knowledge of its skin metabolites exists. Here we present the first comprehensive assessment of the volatile fraction of rabbit skin metabolites using polydimethylsiloxane sorbent patch sampling in conjunction with gas chromatography/mass spectrometry. A collection of compounds that are secreted from rabbit skin was documented, and predominantly acyclic long-chain alkyls and alcohols were detected. We then utilized this animal model to study differences between intact skin and skin with early pressure ulcers, as the latter are a major problem in intensive care units. Four New Zealand female white rabbits underwent ulcer formation on one ear with the other ear as a control. Early-stage ulcers were created with neodymium magnets. Histologic analysis showed acute heterophilic dermatitis, edema, and micro-hemorrhage on the ulcerated ears with normal findings on the control ears. The metabolomic analysis revealed subtle but noticeable differences, with several compounds associated with the oxidative stress-related degradation of lipids found to be present in greater abundances in ulcerated ears. The metabolomic findings correlate with histologic evidence of early-stage ulcers. We postulate that the Leporidae model recapitulated the vascular changes associated with ulcer formation. This study illustrates the potential usefulness of the Leporidae model for skin metabolome studies. Additionally, skin metabolome analysis may enhance an understanding of non-skin sources such as urine or breath.",
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