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Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurata

dc.contributor.authorPoudel, Sunil
dc.contributor.authorIzquierdo, Marisol
dc.contributor.authorCancela, M. Leonor
dc.contributor.authorGavaia, Paulo
dc.date.accessioned2022-04-01T09:39:26Z
dc.date.available2022-04-01T09:39:26Z
dc.date.issued2022-03-09
dc.date.updated2022-03-24T14:47:35Z
dc.description.abstractDoxorubicin 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifierdoi: 10.3390/nu14061154
dc.identifier.citationNutrients 14 (6): 1154 (2022)pt_PT
dc.identifier.doi10.3390/nu14061154pt_PT
dc.identifier.issn2072-6643
dc.identifier.urihttp://hdl.handle.net/10400.1/17745
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationAquaculture meets Biomedicine: Innovation in Skeletal Health research.
dc.relationAlgarve Centre for Marine Sciences
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectOxidative stresspt_PT
dc.subjectResveratrolpt_PT
dc.subjectMitoTEMPOpt_PT
dc.subjectDoxorubicinpt_PT
dc.subjectBone deformitiespt_PT
dc.subjectMineralizationpt_PT
dc.titleReversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus auratapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAquaculture meets Biomedicine: Innovation in Skeletal Health research.
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/766347/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04326%2F2020/PT
oaire.citation.issue6pt_PT
oaire.citation.startPage1154pt_PT
oaire.citation.titleNutrientspt_PT
oaire.citation.volume14pt_PT
oaire.fundingStreamH2020
oaire.fundingStream6817 - DCRRNI ID
person.familyNamePoudel
person.familyNameCancela
person.familyNameGavaia
person.givenNameSunil
person.givenNameM. Leonor
person.givenNamePaulo
person.identifier.ciencia-id8718-1C0C-CBE8
person.identifier.ciencia-idB619-FC16-D007
person.identifier.orcid0000-0002-3750-0071
person.identifier.orcid0000-0003-3114-6662
person.identifier.orcid0000-0002-9582-1957
person.identifier.ridA-6470-2011
person.identifier.scopus-author-id6507104377
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication7937551d-0263-4160-9fc6-952c271f11f1
relation.isAuthorOfPublicationb9bbfe32-3dfe-4131-ad14-a4394008447f
relation.isAuthorOfPublication9dca2139-21a4-4d59-aaf7-531f1033a58e
relation.isAuthorOfPublication.latestForDiscoveryb9bbfe32-3dfe-4131-ad14-a4394008447f
relation.isProjectOfPublication29e15538-1493-4e61-8be8-055155b79344
relation.isProjectOfPublicationfafa76a6-2cd2-4a6d-a3c9-772f34d3b91f
relation.isProjectOfPublication.latestForDiscovery29e15538-1493-4e61-8be8-055155b79344

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