Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurata
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/17745 |
Resumo: | Doxorubicin is a widely used chemotherapeutic drug known to induce bone loss. The mechanism behind doxorubicin-mediated bone loss is unclear, but oxidative stress has been suggested as a potential cause. Antioxidants that can counteract the toxic effect of doxorubicin on the bone would be helpful for the prevention of secondary osteoporosis. We used resveratrol, a natural antioxidant, and MitoTEMPO, a mitochondria-targeted antioxidant, to counteract doxorubicin-induced bone loss and mineralization on <i>Sparus aurata</i> larvae. Doxorubicin supplemented Microdiets increased bone deformities, decreased mineralization, and lipid peroxidation, whereas Resveratrol and MitoTEMPO supplemented microdiets improved mineralization, decreased bone deformities, and reversed the effects of doxorubicin in vivo and in vitro, using osteoblastic VSa13 cells. Partial Least-Squares Discriminant Analysis highlighted differences between groups on the distribution of skeletal anomalies and mineralization of skeleton elements. Calcium and Phosphorus content was negatively affected in the doxorubicin supplemented group. Doxorubicin reduced the mRNA expression of antioxidant genes, including <i>catalase</i>, <i>glutathione peroxidase 1</i>, <i>superoxide dismutase 1</i>, and <i>hsp90</i> suggesting that ROS are central for Doxorubicin-induced bone loss. The mRNA expression of antioxidant genes was significantly increased on resveratrol alone or combined treatment. The length of intestinal villi was increased in response to antioxidants and reduced on doxorubicin. Antioxidant supplements effectively prevent bone deformities and mineralization defects, increase antioxidant response and reverse doxorubicin-induced effects on bone anomalies, mineralization, and oxidative stress. A combined treatment of doxorubicin and antioxidants was beneficial in fish larvae and showed the potential for use in preventing Doxorubicin-induced bone impairment. |
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Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurataOxidative stressResveratrolMitoTEMPODoxorubicinBone deformitiesMineralizationDoxorubicin is a widely used chemotherapeutic drug known to induce bone loss. The mechanism behind doxorubicin-mediated bone loss is unclear, but oxidative stress has been suggested as a potential cause. Antioxidants that can counteract the toxic effect of doxorubicin on the bone would be helpful for the prevention of secondary osteoporosis. We used resveratrol, a natural antioxidant, and MitoTEMPO, a mitochondria-targeted antioxidant, to counteract doxorubicin-induced bone loss and mineralization on <i>Sparus aurata</i> larvae. Doxorubicin supplemented Microdiets increased bone deformities, decreased mineralization, and lipid peroxidation, whereas Resveratrol and MitoTEMPO supplemented microdiets improved mineralization, decreased bone deformities, and reversed the effects of doxorubicin in vivo and in vitro, using osteoblastic VSa13 cells. Partial Least-Squares Discriminant Analysis highlighted differences between groups on the distribution of skeletal anomalies and mineralization of skeleton elements. Calcium and Phosphorus content was negatively affected in the doxorubicin supplemented group. Doxorubicin reduced the mRNA expression of antioxidant genes, including <i>catalase</i>, <i>glutathione peroxidase 1</i>, <i>superoxide dismutase 1</i>, and <i>hsp90</i> suggesting that ROS are central for Doxorubicin-induced bone loss. The mRNA expression of antioxidant genes was significantly increased on resveratrol alone or combined treatment. The length of intestinal villi was increased in response to antioxidants and reduced on doxorubicin. Antioxidant supplements effectively prevent bone deformities and mineralization defects, increase antioxidant response and reverse doxorubicin-induced effects on bone anomalies, mineralization, and oxidative stress. A combined treatment of doxorubicin and antioxidants was beneficial in fish larvae and showed the potential for use in preventing Doxorubicin-induced bone impairment.MDPISapientiaPoudel, SunilIzquierdo, MarisolCancela, M. LeonorGavaia, Paulo2022-04-01T09:39:26Z2022-03-092022-03-24T14:47:35Z2022-03-09T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/17745engNutrients 14 (6): 1154 (2022)2072-664310.3390/nu14061154info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:29:54Zoai:sapientia.ualg.pt:10400.1/17745Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:07:37.104028Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurata |
title |
Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurata |
spellingShingle |
Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurata Poudel, Sunil Oxidative stress Resveratrol MitoTEMPO Doxorubicin Bone deformities Mineralization |
title_short |
Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurata |
title_full |
Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurata |
title_fullStr |
Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurata |
title_full_unstemmed |
Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurata |
title_sort |
Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurata |
author |
Poudel, Sunil |
author_facet |
Poudel, Sunil Izquierdo, Marisol Cancela, M. Leonor Gavaia, Paulo |
author_role |
author |
author2 |
Izquierdo, Marisol Cancela, M. Leonor Gavaia, Paulo |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Poudel, Sunil Izquierdo, Marisol Cancela, M. Leonor Gavaia, Paulo |
dc.subject.por.fl_str_mv |
Oxidative stress Resveratrol MitoTEMPO Doxorubicin Bone deformities Mineralization |
topic |
Oxidative stress Resveratrol MitoTEMPO Doxorubicin Bone deformities Mineralization |
description |
Doxorubicin is a widely used chemotherapeutic drug known to induce bone loss. The mechanism behind doxorubicin-mediated bone loss is unclear, but oxidative stress has been suggested as a potential cause. Antioxidants that can counteract the toxic effect of doxorubicin on the bone would be helpful for the prevention of secondary osteoporosis. We used resveratrol, a natural antioxidant, and MitoTEMPO, a mitochondria-targeted antioxidant, to counteract doxorubicin-induced bone loss and mineralization on <i>Sparus aurata</i> larvae. Doxorubicin supplemented Microdiets increased bone deformities, decreased mineralization, and lipid peroxidation, whereas Resveratrol and MitoTEMPO supplemented microdiets improved mineralization, decreased bone deformities, and reversed the effects of doxorubicin in vivo and in vitro, using osteoblastic VSa13 cells. Partial Least-Squares Discriminant Analysis highlighted differences between groups on the distribution of skeletal anomalies and mineralization of skeleton elements. Calcium and Phosphorus content was negatively affected in the doxorubicin supplemented group. Doxorubicin reduced the mRNA expression of antioxidant genes, including <i>catalase</i>, <i>glutathione peroxidase 1</i>, <i>superoxide dismutase 1</i>, and <i>hsp90</i> suggesting that ROS are central for Doxorubicin-induced bone loss. The mRNA expression of antioxidant genes was significantly increased on resveratrol alone or combined treatment. The length of intestinal villi was increased in response to antioxidants and reduced on doxorubicin. Antioxidant supplements effectively prevent bone deformities and mineralization defects, increase antioxidant response and reverse doxorubicin-induced effects on bone anomalies, mineralization, and oxidative stress. A combined treatment of doxorubicin and antioxidants was beneficial in fish larvae and showed the potential for use in preventing Doxorubicin-induced bone impairment. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-04-01T09:39:26Z 2022-03-09 2022-03-24T14:47:35Z 2022-03-09T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.1/17745 |
url |
http://hdl.handle.net/10400.1/17745 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nutrients 14 (6): 1154 (2022) 2072-6643 10.3390/nu14061154 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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