Pyrroles as a Potential Biomarker for Oxidative Stress Disorders

Author:

Lambert Brett1,Semmler Annalese2ORCID,Beer Cristina3,Voisey Joanne3ORCID

Affiliation:

1. Applied Analytical Laboratories, Logandowns Dr, Meadowbrook, QLD 4131, Australia

2. School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia

3. Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia

Abstract

Redox imbalance or oxidative stress that results from both environmental and genetic factors is observed in patients with schizophrenia. Therefore, identifying markers of oxidative stress in the early stages of psychosis and using antioxidant treatments as an adjuvant to antipsychotics has important implications. The reaction of p-N,N-dimethylaminobenzaldehyde (DMAB) with pyrrole moieties has been well studied for well over a century for use as a marker of oxidative stress dysregulation. Throughout this time, pyrroles have been investigated with varying veracity in urine extracts to identify elevated levels in patients diagnosed with schizophrenia. Since the 1960’s, various claims have been made with respect to what causes the colour change when DMAB is added to urine extracts. Whilst the substances from this reaction have not been fully elucidated, an objective look at most studies indicates that urobilinogen is likely to be one them. Urobilinogen has also been identified as a major interferent in our results. Both pyrroles and urobilinogen condense the DMAB reaction system (form condensation products) and are quite different. The urobilinogen detected in urine forms when gut microflora chemically reduces the bilirubin content of bile acids. In comparison, evidence suggests that the pyrrole fraction originates from the fragmentation of regulatory haem by reactive oxygen species (ROS) such as hydrogen peroxide and super and nitrous oxides. Clinical studies in our laboratories have established that pyrroles as a urine biomarker have specificity in detecting schizophrenia; however, caution must be applied as the readings are subject to interference by other DMAB active compounds that are present, such as urobilinogen. This review highlights the initial chemistry in isolating pyrroles and provides recommendations for standardised laboratory testing to ensure pyrroles are correctly measured and distinguished from other by-products.

Funder

Philanthropic-private

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference32 articles.

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3. Ueber einige Produkte der Steinkohlendestillation;Runge;Ann. Physik.,1834

4. Hydroxy-hemopyrrolenone, not kryptopyrrole, in the urine of schizophrenics and porphyrics;Irvine;Clin. Chem.,1978

5. Malvaria, schizophrenia and the HOD test;Hoffer;Int. J. Neuropsychiatr.,1966

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