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Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity
Doxorubicin (DOX) is an efficient chemotherapeutic agent, but its clinical application is limited by its cardiotoxicity associated with increased oxidative stress. Thus, the combination of DOX and antioxidants has been encouraged. In this study, we evaluated (I) the chemical composition and antioxid...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046128/ https://www.ncbi.nlm.nih.gov/pubmed/30050650 http://dx.doi.org/10.1155/2018/2935051 |
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author | dos Santos, Jéssica Maurino Alfredo, Tamaeh Monteiro Antunes, Katia Ávila da Cunha, Janielle da Silva Melo Costa, Edna Márcia Almeida Lima, Emerson Silva Silva, Denise Brentan Carollo, Carlos Alexandre Schmitz, Wanderlei Onofre Boleti, Ana Paula de Araújo dos Santos, Edson Lucas de Picoli Souza, Kely |
author_facet | dos Santos, Jéssica Maurino Alfredo, Tamaeh Monteiro Antunes, Katia Ávila da Cunha, Janielle da Silva Melo Costa, Edna Márcia Almeida Lima, Emerson Silva Silva, Denise Brentan Carollo, Carlos Alexandre Schmitz, Wanderlei Onofre Boleti, Ana Paula de Araújo dos Santos, Edson Lucas de Picoli Souza, Kely |
author_sort | dos Santos, Jéssica Maurino |
collection | PubMed |
description | Doxorubicin (DOX) is an efficient chemotherapeutic agent, but its clinical application is limited by its cardiotoxicity associated with increased oxidative stress. Thus, the combination of DOX and antioxidants has been encouraged. In this study, we evaluated (I) the chemical composition and antioxidant capacity of aqueous extracts from Guazuma ulmifolia stem bark (GUEsb) and leaves (GUEl) in 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, 2,2′-azobis(2-amidinopropane) dihydrochloride- (AAPH-) or DOX-induced lipid peroxidation inhibition in human blood cells, and intracellular reactive oxygen species (ROS) quantification using the fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) in K562 erythroleukemia cells incubated with GUEsb and stimulated with hydrogen peroxide; (II) the viability of K562 cells and human leukocytes treated with GUEsb in the absence or presence of DOX using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; (III) the acute toxicity of GUEsb; and (IV) the cardioprotective effect of GUEsb in C57Bl/6 mice treated with DOX. The chemical composition indicated the presence of flavan-3-ol derivatives and condensed tannins in GUEsb and glycosylated flavonoids in GUEl. GUEsb and GUEl showed free-radical scavenging antioxidant activity, antihemolytic activity, and AAPH- as well as DOX-induced malondialdehyde content reduction in human erythrocytes. Based on its higher antioxidant potential, GUEsb was selected and subsequently showed intracellular ROS reduction without impairing the chemotherapeutic activity of DOX in K562 cells or inducing leukocyte cell death, but protected them against DOX-induced cell death. Yet, GUEsb did not show in vivo acute toxicity, and it prevented MDA generation in the cardiac tissue of DOX-treated mice, thus demonstrating its cardioprotective effect. Taken together, the results show that GUEsb and GUEl are natural alternatives to treat diseases associated with oxidative stress and that, in particular, GUEsb may play an adjuvant role in DOX chemotherapy. |
format | Online Article Text |
id | pubmed-6046128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-60461282018-07-26 Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity dos Santos, Jéssica Maurino Alfredo, Tamaeh Monteiro Antunes, Katia Ávila da Cunha, Janielle da Silva Melo Costa, Edna Márcia Almeida Lima, Emerson Silva Silva, Denise Brentan Carollo, Carlos Alexandre Schmitz, Wanderlei Onofre Boleti, Ana Paula de Araújo dos Santos, Edson Lucas de Picoli Souza, Kely Oxid Med Cell Longev Research Article Doxorubicin (DOX) is an efficient chemotherapeutic agent, but its clinical application is limited by its cardiotoxicity associated with increased oxidative stress. Thus, the combination of DOX and antioxidants has been encouraged. In this study, we evaluated (I) the chemical composition and antioxidant capacity of aqueous extracts from Guazuma ulmifolia stem bark (GUEsb) and leaves (GUEl) in 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, 2,2′-azobis(2-amidinopropane) dihydrochloride- (AAPH-) or DOX-induced lipid peroxidation inhibition in human blood cells, and intracellular reactive oxygen species (ROS) quantification using the fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) in K562 erythroleukemia cells incubated with GUEsb and stimulated with hydrogen peroxide; (II) the viability of K562 cells and human leukocytes treated with GUEsb in the absence or presence of DOX using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; (III) the acute toxicity of GUEsb; and (IV) the cardioprotective effect of GUEsb in C57Bl/6 mice treated with DOX. The chemical composition indicated the presence of flavan-3-ol derivatives and condensed tannins in GUEsb and glycosylated flavonoids in GUEl. GUEsb and GUEl showed free-radical scavenging antioxidant activity, antihemolytic activity, and AAPH- as well as DOX-induced malondialdehyde content reduction in human erythrocytes. Based on its higher antioxidant potential, GUEsb was selected and subsequently showed intracellular ROS reduction without impairing the chemotherapeutic activity of DOX in K562 cells or inducing leukocyte cell death, but protected them against DOX-induced cell death. Yet, GUEsb did not show in vivo acute toxicity, and it prevented MDA generation in the cardiac tissue of DOX-treated mice, thus demonstrating its cardioprotective effect. Taken together, the results show that GUEsb and GUEl are natural alternatives to treat diseases associated with oxidative stress and that, in particular, GUEsb may play an adjuvant role in DOX chemotherapy. Hindawi 2018-06-28 /pmc/articles/PMC6046128/ /pubmed/30050650 http://dx.doi.org/10.1155/2018/2935051 Text en Copyright © 2018 Jéssica Maurino dos Santos et al. http://creativecommons.org/licenses/by/4.0/ 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 dos Santos, Jéssica Maurino Alfredo, Tamaeh Monteiro Antunes, Katia Ávila da Cunha, Janielle da Silva Melo Costa, Edna Márcia Almeida Lima, Emerson Silva Silva, Denise Brentan Carollo, Carlos Alexandre Schmitz, Wanderlei Onofre Boleti, Ana Paula de Araújo dos Santos, Edson Lucas de Picoli Souza, Kely Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity |
title |
Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity |
title_full |
Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity |
title_fullStr |
Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity |
title_full_unstemmed |
Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity |
title_short |
Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity |
title_sort | guazuma ulmifolia lam. decreases oxidative stress in blood cells and prevents doxorubicin-induced cardiotoxicity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046128/ https://www.ncbi.nlm.nih.gov/pubmed/30050650 http://dx.doi.org/10.1155/2018/2935051 |
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