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Intensification of Doxorubicin-Related Oxidative Stress in the Heart by Hypothyroidism Is Not Related to the Expression of Cytochrome P450 NADPH-Reductase and Inducible Nitric Oxide Synthase, As Well As Activity of Xanthine Oxidase
Cytochrome P450 NADPH-reductase (P450R), inducible synthase (iNOS) and xanthine oxidase play an important role in the antracycline-related cardiotoxicity. The expression of P450R and iNOS is regulated by triiodothyronine. The aim of this study was to evaluate the effect of methimazole-induced hypoth...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432562/ https://www.ncbi.nlm.nih.gov/pubmed/22966413 http://dx.doi.org/10.1155/2012/139327 |
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author | Dudka, Jaroslaw Burdan, Franciszek Korga, Agnieszka Iwan, Magdalena Madej-Czerwonka, Barbara Cendrowska-Pinkosz, Monika Korobowicz-Markiewicz, Agnieszka Jodlowska-Jedrych, Barbara Matysiak, Wlodzimierz |
author_facet | Dudka, Jaroslaw Burdan, Franciszek Korga, Agnieszka Iwan, Magdalena Madej-Czerwonka, Barbara Cendrowska-Pinkosz, Monika Korobowicz-Markiewicz, Agnieszka Jodlowska-Jedrych, Barbara Matysiak, Wlodzimierz |
author_sort | Dudka, Jaroslaw |
collection | PubMed |
description | Cytochrome P450 NADPH-reductase (P450R), inducible synthase (iNOS) and xanthine oxidase play an important role in the antracycline-related cardiotoxicity. The expression of P450R and iNOS is regulated by triiodothyronine. The aim of this study was to evaluate the effect of methimazole-induced hypothyreosis on oxidative stress secondary to doxorubicin administration. 48 hours after methimazole giving cessation, rats were exposed to doxorubicin (2.0, 5.0 and 15 mg/kg). Blood and heart were collected 4, 48 and 96 h after the drug administration. Animals exposed exclusively to doxorubicin or untreated ones were also assessed. The hypothyreosis (0.025% of methimazole) significantly increased the doxorubicin effect on the cardiac carbonyl group and they may increase the glutathione level. An insignificant effect of methimazole was noticed in case of the cardiac lipid peroxidation product, the amount of DNA oxidative damages, iNOS and xanthine oxidase-enzymes responsible for red-ox activation of doxorubicin. However, the concentration of P450R was affected by a lower dose of methimazole in rats administered with doxorubicin. Since in rats receiving doxorubicin changes in oxidative stress caused by methimazole were not accompanied by elevation of bioreductive enzymes, it may be concluded that these changes in the oxidative stress were not related to the tested enzymes. |
format | Online Article Text |
id | pubmed-3432562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-34325622012-09-10 Intensification of Doxorubicin-Related Oxidative Stress in the Heart by Hypothyroidism Is Not Related to the Expression of Cytochrome P450 NADPH-Reductase and Inducible Nitric Oxide Synthase, As Well As Activity of Xanthine Oxidase Dudka, Jaroslaw Burdan, Franciszek Korga, Agnieszka Iwan, Magdalena Madej-Czerwonka, Barbara Cendrowska-Pinkosz, Monika Korobowicz-Markiewicz, Agnieszka Jodlowska-Jedrych, Barbara Matysiak, Wlodzimierz Oxid Med Cell Longev Research Article Cytochrome P450 NADPH-reductase (P450R), inducible synthase (iNOS) and xanthine oxidase play an important role in the antracycline-related cardiotoxicity. The expression of P450R and iNOS is regulated by triiodothyronine. The aim of this study was to evaluate the effect of methimazole-induced hypothyreosis on oxidative stress secondary to doxorubicin administration. 48 hours after methimazole giving cessation, rats were exposed to doxorubicin (2.0, 5.0 and 15 mg/kg). Blood and heart were collected 4, 48 and 96 h after the drug administration. Animals exposed exclusively to doxorubicin or untreated ones were also assessed. The hypothyreosis (0.025% of methimazole) significantly increased the doxorubicin effect on the cardiac carbonyl group and they may increase the glutathione level. An insignificant effect of methimazole was noticed in case of the cardiac lipid peroxidation product, the amount of DNA oxidative damages, iNOS and xanthine oxidase-enzymes responsible for red-ox activation of doxorubicin. However, the concentration of P450R was affected by a lower dose of methimazole in rats administered with doxorubicin. Since in rats receiving doxorubicin changes in oxidative stress caused by methimazole were not accompanied by elevation of bioreductive enzymes, it may be concluded that these changes in the oxidative stress were not related to the tested enzymes. Hindawi Publishing Corporation 2012 2012-08-23 /pmc/articles/PMC3432562/ /pubmed/22966413 http://dx.doi.org/10.1155/2012/139327 Text en Copyright © 2012 Jaroslaw Dudka et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Dudka, Jaroslaw Burdan, Franciszek Korga, Agnieszka Iwan, Magdalena Madej-Czerwonka, Barbara Cendrowska-Pinkosz, Monika Korobowicz-Markiewicz, Agnieszka Jodlowska-Jedrych, Barbara Matysiak, Wlodzimierz Intensification of Doxorubicin-Related Oxidative Stress in the Heart by Hypothyroidism Is Not Related to the Expression of Cytochrome P450 NADPH-Reductase and Inducible Nitric Oxide Synthase, As Well As Activity of Xanthine Oxidase |
title | Intensification of Doxorubicin-Related Oxidative Stress in the Heart by Hypothyroidism Is Not Related to the Expression of Cytochrome P450 NADPH-Reductase and Inducible Nitric Oxide Synthase, As Well As Activity of Xanthine Oxidase |
title_full | Intensification of Doxorubicin-Related Oxidative Stress in the Heart by Hypothyroidism Is Not Related to the Expression of Cytochrome P450 NADPH-Reductase and Inducible Nitric Oxide Synthase, As Well As Activity of Xanthine Oxidase |
title_fullStr | Intensification of Doxorubicin-Related Oxidative Stress in the Heart by Hypothyroidism Is Not Related to the Expression of Cytochrome P450 NADPH-Reductase and Inducible Nitric Oxide Synthase, As Well As Activity of Xanthine Oxidase |
title_full_unstemmed | Intensification of Doxorubicin-Related Oxidative Stress in the Heart by Hypothyroidism Is Not Related to the Expression of Cytochrome P450 NADPH-Reductase and Inducible Nitric Oxide Synthase, As Well As Activity of Xanthine Oxidase |
title_short | Intensification of Doxorubicin-Related Oxidative Stress in the Heart by Hypothyroidism Is Not Related to the Expression of Cytochrome P450 NADPH-Reductase and Inducible Nitric Oxide Synthase, As Well As Activity of Xanthine Oxidase |
title_sort | intensification of doxorubicin-related oxidative stress in the heart by hypothyroidism is not related to the expression of cytochrome p450 nadph-reductase and inducible nitric oxide synthase, as well as activity of xanthine oxidase |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432562/ https://www.ncbi.nlm.nih.gov/pubmed/22966413 http://dx.doi.org/10.1155/2012/139327 |
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