Celastrol efficacy by oral administration in the adjuvant-induced arthritis model

Detalhes bibliográficos
Autor(a) principal: Cascao, Rita
Data de Publicação: 2020
Outros Autores: Vidal, Bruno, Carvalho, Tânia, Lopes, Inês, Romão, Vasco C., Goncalves, Joao, Moita, Luis, Fonseca, João Eurico
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/46663
Resumo: Copyright © 2020 Cascão, Vidal, Carvalho, Lopes, Romão, Goncalves, Moita and Fonseca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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spelling Celastrol efficacy by oral administration in the adjuvant-induced arthritis modelAdjuvant-induced arthritisCelastrolDoseEfficacyRheumatoid arthritisCopyright © 2020 Cascão, Vidal, Carvalho, Lopes, Romão, Goncalves, Moita and Fonseca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Background: We previously demonstrated that celastrol has significant anti-inflammatory and bone protective effects when administered via the intraperitoneal route. For further preclinical evaluation, an effective oral administration of celastrol is crucial. Here we aimed to study the therapeutic dose range for its oral administration. Methods: Celastrol (1-25 μg/g/day, N = 5/group) was administrated orally to female adjuvant-induced arthritis (AIA) rats after 8 days of disease induction for a period of 14 days. A group of healthy (N = 8) and arthritic (N = 15) gender- and age-matched Wistar rats was used as controls. During the treatment period, the inflammatory score, ankle perimeter, and body weight were measured. At the end of the treatment, the animals were sacrificed, blood was collected for clinical pathology, necropsy was performed with collection of internal organs for histopathological analysis, and paw samples were used for disease scoring. Results: Doses higher than 2.5 μg/g/day of celastrol reduced the inflammatory score and ankle swelling, preserved joint structure, halted bone destruction, and diminished the number of synovial CD68+ macrophages. Bone resorption and turnover were also reduced at 5 and 7.5 μg/g/day doses. However, the dose of 7.5 μg/g/day was associated with thymic and liver lesions, and higher doses showed severe toxicity. Conclusion: Oral administration of celastrol above 2.5 μg/g/day ameliorates arthritis. This data supports and gives relevant information for the development of a preclinical test of celastrol in the setting of a chronic model of arthritis since rheumatoid arthritis is a long-term disease.FrontiersRepositório da Universidade de LisboaCascao, RitaVidal, BrunoCarvalho, TâniaLopes, InêsRomão, Vasco C.Goncalves, JoaoMoita, LuisFonseca, João Eurico2021-03-04T17:40:27Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/46663engFront Med (Lausanne). 2020 Sep 8;7:45510.3389/fmed.2020.004552296-858Xinfo: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:RCAAP2023-11-08T16:49:05Zoai:repositorio.ul.pt:10451/46663Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:58:47.618563Repositório 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 Celastrol efficacy by oral administration in the adjuvant-induced arthritis model
title Celastrol efficacy by oral administration in the adjuvant-induced arthritis model
spellingShingle Celastrol efficacy by oral administration in the adjuvant-induced arthritis model
Cascao, Rita
Adjuvant-induced arthritis
Celastrol
Dose
Efficacy
Rheumatoid arthritis
title_short Celastrol efficacy by oral administration in the adjuvant-induced arthritis model
title_full Celastrol efficacy by oral administration in the adjuvant-induced arthritis model
title_fullStr Celastrol efficacy by oral administration in the adjuvant-induced arthritis model
title_full_unstemmed Celastrol efficacy by oral administration in the adjuvant-induced arthritis model
title_sort Celastrol efficacy by oral administration in the adjuvant-induced arthritis model
author Cascao, Rita
author_facet Cascao, Rita
Vidal, Bruno
Carvalho, Tânia
Lopes, Inês
Romão, Vasco C.
Goncalves, Joao
Moita, Luis
Fonseca, João Eurico
author_role author
author2 Vidal, Bruno
Carvalho, Tânia
Lopes, Inês
Romão, Vasco C.
Goncalves, Joao
Moita, Luis
Fonseca, João Eurico
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Cascao, Rita
Vidal, Bruno
Carvalho, Tânia
Lopes, Inês
Romão, Vasco C.
Goncalves, Joao
Moita, Luis
Fonseca, João Eurico
dc.subject.por.fl_str_mv Adjuvant-induced arthritis
Celastrol
Dose
Efficacy
Rheumatoid arthritis
topic Adjuvant-induced arthritis
Celastrol
Dose
Efficacy
Rheumatoid arthritis
description Copyright © 2020 Cascão, Vidal, Carvalho, Lopes, Romão, Goncalves, Moita and Fonseca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-01T00:00:00Z
2021-03-04T17:40:27Z
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/10451/46663
url http://hdl.handle.net/10451/46663
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Front Med (Lausanne). 2020 Sep 8;7:455
10.3389/fmed.2020.00455
2296-858X
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 Frontiers
publisher.none.fl_str_mv Frontiers
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
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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