Regular supplementation with antioxidants rescues Doxorubicin-Induced Bone deformities and mineralization delay in Zebrafish
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/10400.1/18683 |
Resumo: | Osteoporosis is characterized by an abnormal bone structure with low bone mass and degradation of microarchitecture. Oxidative stress induces imbalances in osteoblast and osteoclast activity, leading to bone degradation, a primary cause of secondary osteoporosis. Doxorubicin (DOX) is a widely used chemotherapy drug for treating cancer, known to induce secondary osteoporosis. The mechanism underlying DOX-induced bone loss is still not fully understood, but one of the relevant mechanisms is through a massive accumulation of reactive oxygen and nitrogen species (i.e., ROS and NOS) leading to oxidative stress. We investigated the effects of antioxidants Resveratrol and MitoTEMPO on DOX-induced bone impairment using the zebrafish model. DOX was shown to increase mortality, promote skeletal deformities, induce alterations on intestinal villi, impair growth and mineralization and significantly downregulate osteoblast differentiation markers <i>osteocalcin 2</i> and <i>osterix/sp7</i>. Lipid peroxidation was significantly increased in DOX-supplemented groups as compared to control and antioxidants, suggesting ROS formation as one of the key factors for DOX-induced bone loss. Furthermore, DOX affected mineral contents, suggesting an altered mineral metabolism. However, upon supplementation with antioxidants, DOX-induced effects on mineral content were rescued. Our data show that supplementation with antioxidants effectively improves the overall growth and mineralization in zebrafish and counteracts DOX-induced bone anomalies. |
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Regular supplementation with antioxidants rescues Doxorubicin-Induced Bone deformities and mineralization delay in ZebrafishDoxorubicinMitoTEMPOOxidative stressResveratrolSecondary osteoporosisZebrafishOsteoporosis is characterized by an abnormal bone structure with low bone mass and degradation of microarchitecture. Oxidative stress induces imbalances in osteoblast and osteoclast activity, leading to bone degradation, a primary cause of secondary osteoporosis. Doxorubicin (DOX) is a widely used chemotherapy drug for treating cancer, known to induce secondary osteoporosis. The mechanism underlying DOX-induced bone loss is still not fully understood, but one of the relevant mechanisms is through a massive accumulation of reactive oxygen and nitrogen species (i.e., ROS and NOS) leading to oxidative stress. We investigated the effects of antioxidants Resveratrol and MitoTEMPO on DOX-induced bone impairment using the zebrafish model. DOX was shown to increase mortality, promote skeletal deformities, induce alterations on intestinal villi, impair growth and mineralization and significantly downregulate osteoblast differentiation markers <i>osteocalcin 2</i> and <i>osterix/sp7</i>. Lipid peroxidation was significantly increased in DOX-supplemented groups as compared to control and antioxidants, suggesting ROS formation as one of the key factors for DOX-induced bone loss. Furthermore, DOX affected mineral contents, suggesting an altered mineral metabolism. However, upon supplementation with antioxidants, DOX-induced effects on mineral content were rescued. Our data show that supplementation with antioxidants effectively improves the overall growth and mineralization in zebrafish and counteracts DOX-induced bone anomalies.LA/P/0101/2020MDPISapientiaPoudel, SunilMartins, GilCancela, M. LeonorGavaia, Paulo2022-12-21T09:38:58Z2022-11-232022-12-09T20:23:37Z2022-11-23T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/18683engNutrients 14 (23): 4959 (2022)10.3390/nu142349592072-6643info: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:RCAAP2023-07-24T10:30:54Zoai:sapientia.ualg.pt:10400.1/18683Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:08:22.317950Repositório 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 |
Regular supplementation with antioxidants rescues Doxorubicin-Induced Bone deformities and mineralization delay in Zebrafish |
title |
Regular supplementation with antioxidants rescues Doxorubicin-Induced Bone deformities and mineralization delay in Zebrafish |
spellingShingle |
Regular supplementation with antioxidants rescues Doxorubicin-Induced Bone deformities and mineralization delay in Zebrafish Poudel, Sunil Doxorubicin MitoTEMPO Oxidative stress Resveratrol Secondary osteoporosis Zebrafish |
title_short |
Regular supplementation with antioxidants rescues Doxorubicin-Induced Bone deformities and mineralization delay in Zebrafish |
title_full |
Regular supplementation with antioxidants rescues Doxorubicin-Induced Bone deformities and mineralization delay in Zebrafish |
title_fullStr |
Regular supplementation with antioxidants rescues Doxorubicin-Induced Bone deformities and mineralization delay in Zebrafish |
title_full_unstemmed |
Regular supplementation with antioxidants rescues Doxorubicin-Induced Bone deformities and mineralization delay in Zebrafish |
title_sort |
Regular supplementation with antioxidants rescues Doxorubicin-Induced Bone deformities and mineralization delay in Zebrafish |
author |
Poudel, Sunil |
author_facet |
Poudel, Sunil Martins, Gil Cancela, M. Leonor Gavaia, Paulo |
author_role |
author |
author2 |
Martins, Gil 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 Martins, Gil Cancela, M. Leonor Gavaia, Paulo |
dc.subject.por.fl_str_mv |
Doxorubicin MitoTEMPO Oxidative stress Resveratrol Secondary osteoporosis Zebrafish |
topic |
Doxorubicin MitoTEMPO Oxidative stress Resveratrol Secondary osteoporosis Zebrafish |
description |
Osteoporosis is characterized by an abnormal bone structure with low bone mass and degradation of microarchitecture. Oxidative stress induces imbalances in osteoblast and osteoclast activity, leading to bone degradation, a primary cause of secondary osteoporosis. Doxorubicin (DOX) is a widely used chemotherapy drug for treating cancer, known to induce secondary osteoporosis. The mechanism underlying DOX-induced bone loss is still not fully understood, but one of the relevant mechanisms is through a massive accumulation of reactive oxygen and nitrogen species (i.e., ROS and NOS) leading to oxidative stress. We investigated the effects of antioxidants Resveratrol and MitoTEMPO on DOX-induced bone impairment using the zebrafish model. DOX was shown to increase mortality, promote skeletal deformities, induce alterations on intestinal villi, impair growth and mineralization and significantly downregulate osteoblast differentiation markers <i>osteocalcin 2</i> and <i>osterix/sp7</i>. Lipid peroxidation was significantly increased in DOX-supplemented groups as compared to control and antioxidants, suggesting ROS formation as one of the key factors for DOX-induced bone loss. Furthermore, DOX affected mineral contents, suggesting an altered mineral metabolism. However, upon supplementation with antioxidants, DOX-induced effects on mineral content were rescued. Our data show that supplementation with antioxidants effectively improves the overall growth and mineralization in zebrafish and counteracts DOX-induced bone anomalies. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-12-21T09:38:58Z 2022-11-23 2022-12-09T20:23:37Z 2022-11-23T00:00:00Z |
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/10400.1/18683 |
url |
http://hdl.handle.net/10400.1/18683 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nutrients 14 (23): 4959 (2022) 10.3390/nu14234959 2072-6643 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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MDPI |
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MDPI |
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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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