Targeted Metabolomics Highlights Dramatic Antioxidant Depletion, Increased Oxidative/Nitrosative Stress and Altered Purine and Pyrimidine Concentrations in Serum of Primary Myelofibrosis Patients
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Published:2024-04-19
Issue:4
Volume:13
Page:490
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ISSN:2076-3921
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Container-title:Antioxidants
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language:en
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Short-container-title:Antioxidants
Author:
Mangione Renata12ORCID, Giallongo Cesarina3, Duminuco Andrea4ORCID, La Spina Enrico5, Longhitano Lucia5, Giallongo Sebastiano3, Tibullo Daniele5ORCID, Lazzarino Giuseppe5ORCID, Saab Miriam Wissam5, Sbriglione Arianna5, Palumbo Giuseppe A.3ORCID, Graziani Andrea2ORCID, Alanazi Amer M.6, Di Pietro Valentina78ORCID, Tavazzi Barbara2ORCID, Amorini Angela Maria5ORCID, Lazzarino Giacomo2ORCID
Affiliation:
1. Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of the Sacred Heart of Rome, Largo F. Vito 1, 00168 Rome, Italy 2. Departmental Faculty of Medicine, UniCamillus—Saint Camillus International University of Health and Medical Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy 3. Department of Medical and Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, Division of Hematology, University of Catania, Via S. Sofia 87, 95123 Catania, Italy 4. Hematology Unit with BMT, A.O.U. Policlinico “G.Rodolico-San Marco”, Via S. Sofia 78, 95123 Catania, Italy 5. Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, Via S. Sofia 97, 95123 Catania, Italy 6. Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia 7. Neurotrauma and Ophthalmology Research Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK 8. National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK
Abstract
To date, little is known concerning the circulating levels of biochemically relevant metabolites (antioxidants, oxidative/nitrosative stress biomarkers, purines, and pyrimidines) in patients with primary myelofibrosis (PMF), a rare form of myeloproliferative tumor causing a dramatic decrease in erythropoiesis and angiogenesis. In this study, using a targeted metabolomic approach, serum samples of 22 PMF patients and of 22 control healthy donors were analyzed to quantify the circulating concentrations of hypoxanthine, xanthine, uric acid (as representative purines), uracil, β-pseudouridine, uridine (as representative pyrimidines), reduced glutathione (GSH), ascorbic acid (as two of the main water-soluble antioxidants), malondialdehyde, nitrite, nitrate (as oxidative/nitrosative stress biomarkers) and creatinine, using well-established HPLC method for their determination. Results showed that PMF patients have dramatic depletions of both ascorbic acid and GSH (37.3- and 3.81-times lower circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001), accompanied by significant increases in malondialdehyde (MDA) and nitrite + nitrate (4.73- and 1.66-times higher circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001). Additionally, PMF patients have remarkable alterations of circulating purines, pyrimidines, and creatinine, suggesting potential mitochondrial dysfunctions causing energy metabolism imbalance and consequent increases in these cell energy-related compounds. Overall, these results, besides evidencing previously unknown serum metabolic alterations in PMF patients, suggest that the determination of serum levels of the aforementioned compounds may be useful to evaluate PMF patients on hospital admission for adjunctive therapies aimed at recovering their correct antioxidant status, as well as to monitor patients’ status and potential pharmacological treatments.
Funder
Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Italy King Saud University, Riyadh, Saudi Arabia
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