Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos

Detalhes bibliográficos
Autor(a) principal: Castro, Rondinelle Ribeiro
Data de Publicação: 2008
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
dARK ID: ark:/83112/0013000007n11
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/3935
Resumo: Using the osteoarthritis (OA) model induced by anterior cruciate ligament transection (ACLT) in rats, we have demonstred that guar gum (GG), a galactomannan extracted from Cyamopsis tetragonolobus seeds, displays analgesic activity similar to Hylan G-F 20, a hyaluronate derivate used as local therapy in human OA. In the same model, we objective to develop a parametric biochemical method for joint lesion evaluation, and to investigate the mechanism for analgesia and the chondroprotective effect of GG. Wistar rats subjected to ACLT (OA group) were sacrificed at different endpoints. Joint pain was daily measured using the test for articular incapacitation in rats, until 70 days. Joint lavage was used for NO determination. Articular cartilage was evaluated by the chondroitin-sulfate (CS) content and determination of its molar weight. Histophatologic analysis using the OARSI score system was also performed. Sham-operated groups were used for comparison. In the studies of joint pain, OA groups received indomethacin (2mg/kg/d s.c.), meloxicam (6mg/kg/d i.p.), tadalafil (0.5mg/kg/d p.o.) between days 4 and 7.Morphine (200µg i.art.) was given at day 4 only, 30 min before the pain evaluation. Naloxone (500µg i. art.) was given 15 min prior morphine. Sodium alendronate (30 or 240µg i. art.) was given prophilactically, starting 3 days prior ACLT, and repeated at each 3 days, until day 6. Original or chemically modified GG (100μg/50μl i. art.) was given as a single dose at day 4. Galactose or mannose was co-administred (500μg/50μl i. art.) with original GG. In the study of chondroprotection, GG (100μg/50μl i. art.) was given once weekly, starting at day 14, during 8 weeks. Non-treated animals (NT) received vehicle (saline). OA animals presented maximal joint pain and NO release in the first week. Both CS content and molar weight were higher at day 70 (p<0.05). At this endpoint, important histopathologic changes were found in the OA group. Indomethacin, meloxican, tadalafil and morphine significantly reduced joint pain (p<0.05). Naloxone reverted the effect of morphine. Alendronate prevented the joint pain development. Modified GG structures were unable to promote analgesia. The analgesic effect of unmodified GG could be reverted by galactose (p<0.01), but not by mannose. GG treatment prevented the CS changes, and it reduced the histopatologic lesion (p<0.05). CS changes seem to reflect the tecidual damage, and may be used as an index for the joint lesion. The analgesic efficacy of GG is due to galactose residues. In addition, the chondroprotective effect by GG was demonstrated. This is an important contribution to propose GG as an antiarthrosic drug.
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spelling Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratosEffects of the galactomannan of Cyamopsis tetragonolobus in the osteoarthritis induced by anterior cruciate ligament transection in ratsOsteoartritePolissacarídeosCartilagemFitoterapiaDorUsing the osteoarthritis (OA) model induced by anterior cruciate ligament transection (ACLT) in rats, we have demonstred that guar gum (GG), a galactomannan extracted from Cyamopsis tetragonolobus seeds, displays analgesic activity similar to Hylan G-F 20, a hyaluronate derivate used as local therapy in human OA. In the same model, we objective to develop a parametric biochemical method for joint lesion evaluation, and to investigate the mechanism for analgesia and the chondroprotective effect of GG. Wistar rats subjected to ACLT (OA group) were sacrificed at different endpoints. Joint pain was daily measured using the test for articular incapacitation in rats, until 70 days. Joint lavage was used for NO determination. Articular cartilage was evaluated by the chondroitin-sulfate (CS) content and determination of its molar weight. Histophatologic analysis using the OARSI score system was also performed. Sham-operated groups were used for comparison. In the studies of joint pain, OA groups received indomethacin (2mg/kg/d s.c.), meloxicam (6mg/kg/d i.p.), tadalafil (0.5mg/kg/d p.o.) between days 4 and 7.Morphine (200µg i.art.) was given at day 4 only, 30 min before the pain evaluation. Naloxone (500µg i. art.) was given 15 min prior morphine. Sodium alendronate (30 or 240µg i. art.) was given prophilactically, starting 3 days prior ACLT, and repeated at each 3 days, until day 6. Original or chemically modified GG (100μg/50μl i. art.) was given as a single dose at day 4. Galactose or mannose was co-administred (500μg/50μl i. art.) with original GG. In the study of chondroprotection, GG (100μg/50μl i. art.) was given once weekly, starting at day 14, during 8 weeks. Non-treated animals (NT) received vehicle (saline). OA animals presented maximal joint pain and NO release in the first week. Both CS content and molar weight were higher at day 70 (p<0.05). At this endpoint, important histopathologic changes were found in the OA group. Indomethacin, meloxican, tadalafil and morphine significantly reduced joint pain (p<0.05). Naloxone reverted the effect of morphine. Alendronate prevented the joint pain development. Modified GG structures were unable to promote analgesia. The analgesic effect of unmodified GG could be reverted by galactose (p<0.01), but not by mannose. GG treatment prevented the CS changes, and it reduced the histopatologic lesion (p<0.05). CS changes seem to reflect the tecidual damage, and may be used as an index for the joint lesion. The analgesic efficacy of GG is due to galactose residues. In addition, the chondroprotective effect by GG was demonstrated. This is an important contribution to propose GG as an antiarthrosic drug.No modelo de osteoartrite (OA) induzida por transecção do ligamento cruzado anterior em ratos (TLCA), havíamos demonstrado que a goma guar (GG), uma galactomanana extraída das sementes de Cyamopsis tetragonolobus goma guar, apresenta atividade analgésica em magnitude semelhante à exibida pelo Hilano G-F 20, um derivado do ácido hialurônico utilizado em terapia intra-articular da OA humana. Utilizando o referido modelo, objetivamos desenvolver um métido bioquímico paramétrico para avaliação da lesão articular no referido modelo, e investigar o mecanismo para a analgesia e a eficácia condroprotetora da GG. Ratos Wistar submetidos à TLCA (grupo OA) foram sacrificados em diferentes períodos. A dor articular foi avaliada diariamente pelo teste de incapacitação para ratos, por até 70 dias. O lavado articular foi usado para determinação da liberação de NO. A cartilagem foi avaliada pela determinação do teor de condrotin-sulfato (CS) na matriz, além da avaliação da massa molar do mesmo. A lesão articular foi avaliada também por análise histopatológica, segundo os escores OARSI. Grupos falso-operados (sham) foram utilizados para comparação. Para estudos sobre a dor articular, animais do grupo OA receberam terapeuticamente indometacina (2mg/kg/d s.c.), meloxicam (6mg/kg/d i.p.), ou tadalafila (0,5mg/kg/d p.o.), do quarto ao sétimo dias. Morfina (200µg i. art.) foi administrada apenas no quarto dia, 30 min antes da avaliação da dor. Naloxona (500µg i. art.) foi administrada 15 min antes de morfina. Alendronato sódico (30 ou 240µg/kg s.c.) foi administrado profilaticamente três dias antes da indução, e repetido a cada três dias, até o sexto dia. GG original ou quimicamente modificada foi administrada em dose única no quarto dia (100μg/50μl i. art.). Galactose ou manose (500μg/50μl i. art.) foram co-administrados à GG original. Para avaliação sobre a lesão da cartilagem, GG (100μg/50μl i. art) foi administrada como dose única semanal, do 14º ao 63º dias. Animais não tratados (NT) receberam veículo (salina) nas respectivas vias. O grupo OA apresentou dor articular máxima durante a primeira semana, período no qual houve a maior liberação de NO. 70 dias após TLCA, o teor e a massa molar do CS da matriz da cartilagem mostraram-se ambos aumentados (p<0,05). Importantes alterações histopatológicas foram encontradas no grupo OA nesse período. Indometacina, meloxicam, tadalafila e morfina reduziram significantemente a dor (p<0,05), sendo o efeito desta última revertido por naloxona. Alendronato sódico preveniu a ocorrência da dor. As estruturas modificadas de GG não exibiram eficácia analgésica. Galactose, mas não manose, reverteu significativamente o efeito analgésico da GG não-modificada (p<0,01). GG preveniu as alterações do CS da cartilagem, e reduziu significativamente a lesão histopatológica (p<0,05). As alterações sofridas pelo CS parecem refletir o dano tecidual, validando tal metodologia para avaliação da lesão estrutural. A eficácia analgésica da GG decorre de um efeito farmacológico dependente de galactose. Mais ainda, demonstramos a eficácia condroprotetora in vivo para a GG, indispendável para sua validação como droga anti-artrósica.Rocha , Francisco Airton Castro daCastro, Rondinelle Ribeiro2012-10-18T12:04:07Z2012-10-18T12:04:07Z2008info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfCASTRO, R. R. Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos. 2008. 115 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2008.http://www.repositorio.ufc.br/handle/riufc/3935ark:/83112/0013000007n11porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2021-06-29T12:37:42Zoai:repositorio.ufc.br:riufc/3935Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:33:43.996416Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos
Effects of the galactomannan of Cyamopsis tetragonolobus in the osteoarthritis induced by anterior cruciate ligament transection in rats
title Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos
spellingShingle Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos
Castro, Rondinelle Ribeiro
Osteoartrite
Polissacarídeos
Cartilagem
Fitoterapia
Dor
title_short Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos
title_full Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos
title_fullStr Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos
title_full_unstemmed Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos
title_sort Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos
author Castro, Rondinelle Ribeiro
author_facet Castro, Rondinelle Ribeiro
author_role author
dc.contributor.none.fl_str_mv Rocha , Francisco Airton Castro da
dc.contributor.author.fl_str_mv Castro, Rondinelle Ribeiro
dc.subject.por.fl_str_mv Osteoartrite
Polissacarídeos
Cartilagem
Fitoterapia
Dor
topic Osteoartrite
Polissacarídeos
Cartilagem
Fitoterapia
Dor
description Using the osteoarthritis (OA) model induced by anterior cruciate ligament transection (ACLT) in rats, we have demonstred that guar gum (GG), a galactomannan extracted from Cyamopsis tetragonolobus seeds, displays analgesic activity similar to Hylan G-F 20, a hyaluronate derivate used as local therapy in human OA. In the same model, we objective to develop a parametric biochemical method for joint lesion evaluation, and to investigate the mechanism for analgesia and the chondroprotective effect of GG. Wistar rats subjected to ACLT (OA group) were sacrificed at different endpoints. Joint pain was daily measured using the test for articular incapacitation in rats, until 70 days. Joint lavage was used for NO determination. Articular cartilage was evaluated by the chondroitin-sulfate (CS) content and determination of its molar weight. Histophatologic analysis using the OARSI score system was also performed. Sham-operated groups were used for comparison. In the studies of joint pain, OA groups received indomethacin (2mg/kg/d s.c.), meloxicam (6mg/kg/d i.p.), tadalafil (0.5mg/kg/d p.o.) between days 4 and 7.Morphine (200µg i.art.) was given at day 4 only, 30 min before the pain evaluation. Naloxone (500µg i. art.) was given 15 min prior morphine. Sodium alendronate (30 or 240µg i. art.) was given prophilactically, starting 3 days prior ACLT, and repeated at each 3 days, until day 6. Original or chemically modified GG (100μg/50μl i. art.) was given as a single dose at day 4. Galactose or mannose was co-administred (500μg/50μl i. art.) with original GG. In the study of chondroprotection, GG (100μg/50μl i. art.) was given once weekly, starting at day 14, during 8 weeks. Non-treated animals (NT) received vehicle (saline). OA animals presented maximal joint pain and NO release in the first week. Both CS content and molar weight were higher at day 70 (p<0.05). At this endpoint, important histopathologic changes were found in the OA group. Indomethacin, meloxican, tadalafil and morphine significantly reduced joint pain (p<0.05). Naloxone reverted the effect of morphine. Alendronate prevented the joint pain development. Modified GG structures were unable to promote analgesia. The analgesic effect of unmodified GG could be reverted by galactose (p<0.01), but not by mannose. GG treatment prevented the CS changes, and it reduced the histopatologic lesion (p<0.05). CS changes seem to reflect the tecidual damage, and may be used as an index for the joint lesion. The analgesic efficacy of GG is due to galactose residues. In addition, the chondroprotective effect by GG was demonstrated. This is an important contribution to propose GG as an antiarthrosic drug.
publishDate 2008
dc.date.none.fl_str_mv 2008
2012-10-18T12:04:07Z
2012-10-18T12:04:07Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv CASTRO, R. R. Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos. 2008. 115 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2008.
http://www.repositorio.ufc.br/handle/riufc/3935
dc.identifier.dark.fl_str_mv ark:/83112/0013000007n11
identifier_str_mv CASTRO, R. R. Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos. 2008. 115 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2008.
ark:/83112/0013000007n11
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