Celastrol Efficacy by Oral Administration in the Adjuvant-Induced Arthritis Model
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 do...
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmed.2020.00455/full |
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| author | Rita Cascão Bruno Vidal Tânia Carvalho Inês Pascoal Lopes Vasco C. Romão Vasco C. Romão João Goncalves Luis Ferreira Moita João Eurico Fonseca João Eurico Fonseca |
| author_facet | Rita Cascão Bruno Vidal Tânia Carvalho Inês Pascoal Lopes Vasco C. Romão Vasco C. Romão João Goncalves Luis Ferreira Moita João Eurico Fonseca João Eurico Fonseca |
| author_sort | Rita Cascão |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T06:15:12Z |
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| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-20T06:15:12Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-94e4c20a4ba642e19a8e7cbc6236a3ab2022-12-21T19:50:33ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2020-09-01710.3389/fmed.2020.00455519381Celastrol Efficacy by Oral Administration in the Adjuvant-Induced Arthritis ModelRita Cascão0Bruno Vidal1Tânia Carvalho2Inês Pascoal Lopes3Vasco C. Romão4Vasco C. Romão5João Goncalves6Luis Ferreira Moita7João Eurico Fonseca8João Eurico Fonseca9Unidade de Investigação em Reumatologia, Faculdade de Medicina, Instituto de Medicina Molecular-João Lobo Antunes, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, PortugalUnidade de Investigação em Reumatologia, Faculdade de Medicina, Instituto de Medicina Molecular-João Lobo Antunes, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, PortugalComparative Pathology Unit, Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, PortugalUnidade de Investigação em Reumatologia, Faculdade de Medicina, Instituto de Medicina Molecular-João Lobo Antunes, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, PortugalUnidade de Investigação em Reumatologia, Faculdade de Medicina, Instituto de Medicina Molecular-João Lobo Antunes, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, PortugalServiço de Reumatologia e Doenças Ósseas Metabólicas, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, PortugalFaculdade de Farmácia, iMed – Research Institute of Medicines, Universidade de Lisboa, Lisbon, PortugalInnate Immunity and Inflammation Laboratory, Instituto Gulbenkian de Ciência, Oeiras, PortugalUnidade de Investigação em Reumatologia, Faculdade de Medicina, Instituto de Medicina Molecular-João Lobo Antunes, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, PortugalServiço de Reumatologia e Doenças Ósseas Metabólicas, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, PortugalBackground: 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.https://www.frontiersin.org/article/10.3389/fmed.2020.00455/fullrheumatoid arthritisadjuvant-induced arthritiscelastroldoseefficacy |
| spellingShingle | Rita Cascão Bruno Vidal Tânia Carvalho Inês Pascoal Lopes Vasco C. Romão Vasco C. Romão João Goncalves Luis Ferreira Moita João Eurico Fonseca João Eurico Fonseca Celastrol Efficacy by Oral Administration in the Adjuvant-Induced Arthritis Model Frontiers in Medicine rheumatoid arthritis adjuvant-induced arthritis celastrol dose efficacy |
| title | 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_short | Celastrol Efficacy by Oral Administration in the Adjuvant-Induced Arthritis Model |
| title_sort | celastrol efficacy by oral administration in the adjuvant induced arthritis model |
| topic | rheumatoid arthritis adjuvant-induced arthritis celastrol dose efficacy |
| url | https://www.frontiersin.org/article/10.3389/fmed.2020.00455/full |
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