Pyrroles as a Potential Biomarker for Oxidative Stress Disorders

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.

Molecular Mechanisms Provide a Landscape for Biomarker Selection for Schizophrenia and Schizoaffective Psychosis

“…High levels of this molecule have been detected in the urine of patients with schizophrenia and particularly in those who do not possess the homozygous MTHFR 677 polymorphism [81,126]. Elevated urine HPL levels are reportedly reduced by vitamin B6 (PLP) and zinc supplementation, though the exact mechanism of this effect is yet to be established [127]. Given the relevance of many of the above-discussed downstream effects of the serine-glycine pathway for schizophrenia, serine and glycine and HPL have potential roles as biomarkers for schizophrenia, and preliminary research on their role in this disorder has indeed been reported in the literature [128].…”

Metabolomic Alterations of Volatile Organic Compounds and Bile Acids as Biomarkers of Microbial Shifts in a Murine Model of Short Bowel Syndrome

“…Pyrrole was the only VOC that we found to be significantly decreased in the fecal headspace of SBS animals. The substance was first comprehensively studied in 1938 [43]. Pyrroles are characterized by a ring structure composed of four carbon atoms and one nitrogen atom.…”

Molecular Mechanism Biomarkers Predict Diagnosis in Schizophrenia and Schizoaffective Psychosis, with Implications for Treatment

“…High levels of this molecule leads to metabolic crisis in mitochondria [60]. High levels of HPL have been detected in the urine of patients with schizophrenia who do not possess the homozygous MTHFR 677 polymorphism [61], and significant correlates for heightened HPL have also been linked to multiple symptoms of schizophrenia [15,45,62,63].…”