Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics
Background: Schizophrenia is associated with a deficiency of dietary antioxidants like vitamin B6, B9, and B12 resulting in defective methylation leading to hyperhomocysteinemia. Hyperhomocysteinemia causes mitochondrial DNA damage, oxidative stress, vascular damage, and lipid peroxidation. Oxidativ...
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Frontiers Media S.A.
2021-04-01
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Series: | Frontiers in Pharmacology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.646287/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mahmood Rasool Mahmood Rasool Arif Malik Shamaila Saleem Muhammad Abdul Basit Ashraf Altaf Qadir Khan Sulayman Waquar Ayesha Zahid Sumaira Shaheen Muhammad Abu-Elmagd Muhammad Abu-Elmagd Kalamegam Gauthaman Kalamegam Gauthaman Peter Natesan Pushparaj Peter Natesan Pushparaj |
spellingShingle |
Mahmood Rasool Mahmood Rasool Arif Malik Shamaila Saleem Muhammad Abdul Basit Ashraf Altaf Qadir Khan Sulayman Waquar Ayesha Zahid Sumaira Shaheen Muhammad Abu-Elmagd Muhammad Abu-Elmagd Kalamegam Gauthaman Kalamegam Gauthaman Peter Natesan Pushparaj Peter Natesan Pushparaj Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics Frontiers in Pharmacology schizophrenia hyperhomocysteinemia oxidative stress autoimmune thyroid diseases biomarkers antioxidants |
author_facet |
Mahmood Rasool Mahmood Rasool Arif Malik Shamaila Saleem Muhammad Abdul Basit Ashraf Altaf Qadir Khan Sulayman Waquar Ayesha Zahid Sumaira Shaheen Muhammad Abu-Elmagd Muhammad Abu-Elmagd Kalamegam Gauthaman Kalamegam Gauthaman Peter Natesan Pushparaj Peter Natesan Pushparaj |
author_sort |
Mahmood Rasool |
title |
Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics |
title_short |
Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics |
title_full |
Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics |
title_fullStr |
Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics |
title_full_unstemmed |
Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics |
title_sort |
role of oxidative stress and the identification of biomarkers associated with thyroid dysfunction in schizophrenics |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-04-01 |
description |
Background: Schizophrenia is associated with a deficiency of dietary antioxidants like vitamin B6, B9, and B12 resulting in defective methylation leading to hyperhomocysteinemia. Hyperhomocysteinemia causes mitochondrial DNA damage, oxidative stress, vascular damage, and lipid peroxidation. Oxidative stress and increase in reactive oxygen species result in 8-oxodG production which induces apoptosis of both astrocytes and thyrocytes thus predisposing them to thyroid dysfunction and neurodegeneration. Furthermore, the presence of excessive free radicals increases thyroid thermogenesis causing hyperthyroidism or its excess may cause hypothyroidism by inhibiting iodide uptake. In the present study, we evaluated the various biomarkers associated with thyroid dysfunction in schizophrenics.Materials and Methods: 288 patients suffering from schizophrenia and 100 control subjects were screened for liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). Also, the stress markers, namely malondialdehyde (MDA), homocysteine, cysteine, methionine, the thyroid profile including triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), thyroxine peroxide antibody (TPO-Ab); TSH receptor-Ab (TSHr-Ab), dietary antioxidants, lipids, cytokines, aminoacids and hormones, vitamins and trace elements, and other biochemical parameters.Results: The LFTs showed elevated levels of ALT (45.57 ± 4.87 Vs. 26.41 ± 3.76 U/L), AST (40.55 ± 1.34 Vs. 21.92 ± 3.65 U/L), ALP (121.54 ± 4.87 Vs. 83.76 ± 5.87 U/L), and total bilirubin (2.63 ± 0.987 Vs. 1.10 ± 0.056 mg/dl), in schizophrenics than controls. Increased levels of MDA (3.71 ± 0.967 Vs. 1.68 ± 0.099) and homocysteine (17.56 ± 2.612 Vs. 6.96 ± 1.987 μmol/L were observed in schizophrenics compared to the controls, indicating increased stress. Levels of cysteine and methionine were decreased in schizophrenics than the controls (1.08 ± 0.089 Vs. 4.87 ± .924 μmol/L and 17.87 ± 1.23 Vs. 99.20 ± 5.36 μmol/L). The levels of TPO-Ab (IU/ml), Tg-Ab (pmol/L), and TSHr-Ab (IU/L) were observed to be higher in the patients’ group as compared to control subjects (9.84 ± 2.56 Vs. 5.81 ± 1.98, 55.50 ± 2.98 Vs. 32.95 ± 2.87 and 2.95 ± 0.0045 Vs. 1.44 ± 0.0023 respectively). Levels of Vitamin B6, B9, and B12 were also significantly decreased in the patients compared to the healthy controls.Conclusion: The schizophrenics, demonstrated altered liver function, increased stress markers, and decreased dietary antioxidants. Reduced primary and secondary antioxidant levels, may result in hyperhomocysteinemia and cause further DNA and mitochondrial damage. Therefore, homocysteine and/or prolactin levels may serve as candidate prognostic markers for schizophrenia. Also, both neurological symptoms and the susceptibility to thyroid disorders may be prevented in the initial stages of this debilitating disorder by appropriate dietary supplementation of antioxidants which can rectify a reduction in primary and secondary antioxidants, and disturbed prolactin-serotonin-dopamine interactions in schizophrenics. |
topic |
schizophrenia hyperhomocysteinemia oxidative stress autoimmune thyroid diseases biomarkers antioxidants |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.646287/full |
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doaj-dd068b6c894c42de9bea3b4d2c9d115b2021-04-29T06:23:10ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-04-011210.3389/fphar.2021.646287646287Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in SchizophrenicsMahmood Rasool0Mahmood Rasool1Arif Malik2Shamaila Saleem3Muhammad Abdul Basit Ashraf4Altaf Qadir Khan5Sulayman Waquar6Ayesha Zahid7Sumaira Shaheen8Muhammad Abu-Elmagd9Muhammad Abu-Elmagd10Kalamegam Gauthaman11Kalamegam Gauthaman12Peter Natesan Pushparaj13Peter Natesan Pushparaj14Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi ArabiaCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi ArabiaInstitute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, PakistanUniversity College of Medicine and Dentistry, The University of Lahore, Lahore, PakistanUniversity College of Medicine and Dentistry, The University of Lahore, Lahore, PakistanDepartment of Psychiatry, Ameer-Ud-Din Medical College, Lahore, Lahore, PakistanInstitute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, PakistanInstitute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, PakistanCenter for Research in Molecular Medicine, The University of Lahore, Lahore, PakistanDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi ArabiaCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi ArabiaCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi ArabiaCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi ArabiaBackground: Schizophrenia is associated with a deficiency of dietary antioxidants like vitamin B6, B9, and B12 resulting in defective methylation leading to hyperhomocysteinemia. Hyperhomocysteinemia causes mitochondrial DNA damage, oxidative stress, vascular damage, and lipid peroxidation. Oxidative stress and increase in reactive oxygen species result in 8-oxodG production which induces apoptosis of both astrocytes and thyrocytes thus predisposing them to thyroid dysfunction and neurodegeneration. Furthermore, the presence of excessive free radicals increases thyroid thermogenesis causing hyperthyroidism or its excess may cause hypothyroidism by inhibiting iodide uptake. In the present study, we evaluated the various biomarkers associated with thyroid dysfunction in schizophrenics.Materials and Methods: 288 patients suffering from schizophrenia and 100 control subjects were screened for liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). Also, the stress markers, namely malondialdehyde (MDA), homocysteine, cysteine, methionine, the thyroid profile including triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), thyroxine peroxide antibody (TPO-Ab); TSH receptor-Ab (TSHr-Ab), dietary antioxidants, lipids, cytokines, aminoacids and hormones, vitamins and trace elements, and other biochemical parameters.Results: The LFTs showed elevated levels of ALT (45.57 ± 4.87 Vs. 26.41 ± 3.76 U/L), AST (40.55 ± 1.34 Vs. 21.92 ± 3.65 U/L), ALP (121.54 ± 4.87 Vs. 83.76 ± 5.87 U/L), and total bilirubin (2.63 ± 0.987 Vs. 1.10 ± 0.056 mg/dl), in schizophrenics than controls. Increased levels of MDA (3.71 ± 0.967 Vs. 1.68 ± 0.099) and homocysteine (17.56 ± 2.612 Vs. 6.96 ± 1.987 μmol/L were observed in schizophrenics compared to the controls, indicating increased stress. Levels of cysteine and methionine were decreased in schizophrenics than the controls (1.08 ± 0.089 Vs. 4.87 ± .924 μmol/L and 17.87 ± 1.23 Vs. 99.20 ± 5.36 μmol/L). The levels of TPO-Ab (IU/ml), Tg-Ab (pmol/L), and TSHr-Ab (IU/L) were observed to be higher in the patients’ group as compared to control subjects (9.84 ± 2.56 Vs. 5.81 ± 1.98, 55.50 ± 2.98 Vs. 32.95 ± 2.87 and 2.95 ± 0.0045 Vs. 1.44 ± 0.0023 respectively). Levels of Vitamin B6, B9, and B12 were also significantly decreased in the patients compared to the healthy controls.Conclusion: The schizophrenics, demonstrated altered liver function, increased stress markers, and decreased dietary antioxidants. Reduced primary and secondary antioxidant levels, may result in hyperhomocysteinemia and cause further DNA and mitochondrial damage. Therefore, homocysteine and/or prolactin levels may serve as candidate prognostic markers for schizophrenia. Also, both neurological symptoms and the susceptibility to thyroid disorders may be prevented in the initial stages of this debilitating disorder by appropriate dietary supplementation of antioxidants which can rectify a reduction in primary and secondary antioxidants, and disturbed prolactin-serotonin-dopamine interactions in schizophrenics.https://www.frontiersin.org/articles/10.3389/fphar.2021.646287/fullschizophreniahyperhomocysteinemiaoxidative stressautoimmune thyroid diseasesbiomarkersantioxidants |