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

Detalhes bibliográficos
Autor(a) principal: Rondinelle Ribeiro Castro
Data de Publicação: 2008
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFC
Texto Completo: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=1484
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 (200Âg i.art.) was given at day 4 only, 30 min before the pain evaluation. Naloxone (500Âg i. art.) was given 15 min prior morphine. Sodium alendronate (30 or 240Âg i. art.) was given prophilactically, starting 3 days prior ACLT, and repeated at each 3 days, until day 6. Original or chemically modified GG (100&#956;g/50&#956;l i. art.) was given as a single dose at day 4. Galactose or mannose was co-administred (500&#956;g/50&#956;l i. art.) with original GG. In the study of chondroprotection, GG (100&#956;g/50&#956;l 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 info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisEfeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecÃÃo do ligamento cruzado anterior em ratosEffects of the galactomannan of Cyamopsis tetragonolobus in the osteoarthritis induced by anterior cruciate ligament transection in rats 2008-04-15Francisco Airton Castro da Rocha23373474353http://lattes.cnpq.br/4916026652021507Marcus Raimundo Vale07574169420http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4783813Z0Ana Maria Sampaio Assereuy03978990253http://lattes.cnpq.br/6315343480676626 Paulo AntÃnio de Souza MourÃo53984633815Judith Pessoa de Andrade Feitosa04522036353http://lattes.cnpq.br/560736678214447283901230378http://lattes.cnpq.br/9194176846008423Rondinelle Ribeiro CastroUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em FarmacologiaUFCBROsteoartrite PolissacarÃdeos Dor Cartilagem Gomas VegetaisOsteoarthritis Polysaccharides Pain Cartilage Plant GumsFARMACOLOGIAUsing 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 (200Âg i.art.) was given at day 4 only, 30 min before the pain evaluation. Naloxone (500Âg i. art.) was given 15 min prior morphine. Sodium alendronate (30 or 240Âg i. art.) was given prophilactically, starting 3 days prior ACLT, and repeated at each 3 days, until day 6. Original or chemically modified GG (100&#956;g/50&#956;l i. art.) was given as a single dose at day 4. Galactose or mannose was co-administred (500&#956;g/50&#956;l i. art.) with original GG. In the study of chondroprotection, GG (100&#956;g/50&#956;l 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 drugNo modelo de osteoartrite (OA) induzida por transecÃÃo do ligamento cruzado anterior em ratos (TLCA), havÃamos demonstrado que a goma guar (GG), uma galactomanana extraÃda das sementes de Cyamopsis tetragonolobus goma guar, apresenta atividade analgÃsica em magnitude semelhante à exibida pelo Hilano G-F 20, um derivado do Ãcido hialurÃnico utilizado em terapia intra-articular da OA humana. Utilizando o referido modelo, objetivamos desenvolver um mÃtido bioquÃmico paramÃtrico para avaliaÃÃo da lesÃo articular no referido modelo, e investigar o mecanismo para a analgesia e a eficÃcia condroprotetora da GG. Ratos Wistar submetidos à TLCA (grupo OA) foram sacrificados em diferentes perÃodos. A dor articular foi avaliada diariamente pelo teste de incapacitaÃÃo para ratos, por atà 70 dias. O lavado articular foi usado para determinaÃÃo da liberaÃÃo de NO. A cartilagem foi avaliada pela determinaÃÃo do teor de condrotin-sulfato (CS) na matriz, alÃm da avaliaÃÃo da massa molar do mesmo. A lesÃo articular foi avaliada tambÃm por anÃlise histopatolÃgica, segundo os escores OARSI. Grupos falso-operados (sham) foram utilizados para comparaÃÃo. 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 sÃtimo dias. Morfina (200Âg i. art.) foi administrada apenas no quarto dia, 30 min antes da avaliaÃÃo da dor. Naloxona (500Âg i. art.) foi administrada 15 min antes de morfina. Alendronato sÃdico (30 ou 240Âg/kg s.c.) foi administrado profilaticamente trÃs dias antes da induÃÃo, e repetido a cada trÃs dias, atà o sexto dia. GG original ou quimicamente modificada foi administrada em dose Ãnica no quarto dia (100&#956;g/50&#956;l i. art.). Galactose ou manose (500&#956;g/50&#956;l i. art.) foram co-administrados à GG original. Para avaliaÃÃo sobre a lesÃo da cartilagem, GG (100&#956;g/50&#956;l i. art) foi administrada como dose Ãnica semanal, do 14 ao 63 dias. Animais nÃo tratados (NT) receberam veÃculo (salina) nas respectivas vias. O grupo OA apresentou dor articular mÃxima durante a primeira semana, perÃodo no qual houve a maior liberaÃÃo de NO. 70 dias apÃs TLCA, o teor e a massa molar do CS da matriz da cartilagem mostraram-se ambos aumentados (p<0,05). Importantes alteraÃÃes histopatolÃgicas foram encontradas no grupo OA nesse perÃodo. Indometacina, meloxicam, tadalafila e morfina reduziram significantemente a dor (p<0,05), sendo o efeito desta Ãltima revertido por naloxona. Alendronato sÃdico preveniu a ocorrÃncia da dor. As estruturas modificadas de GG nÃo exibiram eficÃcia analgÃsica. Galactose, mas nÃo manose, reverteu significativamente o efeito analgÃsico da GG nÃo-modificada (p<0,01). GG preveniu as alteraÃÃes do CS da cartilagem, e reduziu significativamente a lesÃo histopatolÃgica (p<0,05). As alteraÃÃes sofridas pelo CS parecem refletir o dano tecidual, validando tal metodologia para avaliaÃÃo da lesÃo estrutural. A eficÃcia analgÃsica da GG decorre de um efeito farmacolÃgico dependente de galactose. Mais ainda, demonstramos a eficÃcia condroprotetora in vivo para a GG, indispendÃvel para sua validaÃÃo como droga anti-artrÃsica.CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superiorhttp://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=1484application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:14:28Zmail@mail.com -
dc.title.pt.fl_str_mv Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecÃÃo do ligamento cruzado anterior em ratos
dc.title.alternative..fl_str_mv 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 transecÃÃo do ligamento cruzado anterior em ratos
spellingShingle Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecÃÃo do ligamento cruzado anterior em ratos
Rondinelle Ribeiro Castro
Osteoartrite
PolissacarÃdeos
Dor
Cartilagem
Gomas Vegetais
Osteoarthritis
Polysaccharides
Pain
Cartilage
Plant Gums
FARMACOLOGIA
title_short Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecÃÃo do ligamento cruzado anterior em ratos
title_full Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecÃÃo do ligamento cruzado anterior em ratos
title_fullStr Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecÃÃo do ligamento cruzado anterior em ratos
title_full_unstemmed Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecÃÃo do ligamento cruzado anterior em ratos
title_sort Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecÃÃo do ligamento cruzado anterior em ratos
author Rondinelle Ribeiro Castro
author_facet Rondinelle Ribeiro Castro
author_role author
dc.contributor.advisor1.fl_str_mv Francisco Airton Castro da Rocha
dc.contributor.advisor1ID.fl_str_mv 23373474353
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/4916026652021507
dc.contributor.referee1.fl_str_mv Marcus Raimundo Vale
dc.contributor.referee1ID.fl_str_mv 07574169420
dc.contributor.referee1Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4783813Z0
dc.contributor.referee2.fl_str_mv Ana Maria Sampaio Assereuy
dc.contributor.referee2ID.fl_str_mv 03978990253
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/6315343480676626
dc.contributor.referee3.fl_str_mv Paulo AntÃnio de Souza MourÃo
dc.contributor.referee3ID.fl_str_mv 53984633815
dc.contributor.referee4.fl_str_mv Judith Pessoa de Andrade Feitosa
dc.contributor.referee4ID.fl_str_mv 04522036353
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/5607366782144472
dc.contributor.authorID.fl_str_mv 83901230378
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/9194176846008423
dc.contributor.author.fl_str_mv Rondinelle Ribeiro Castro
contributor_str_mv Francisco Airton Castro da Rocha
Marcus Raimundo Vale
Ana Maria Sampaio Assereuy
Paulo AntÃnio de Souza MourÃo
Judith Pessoa de Andrade Feitosa
dc.subject.por.fl_str_mv Osteoartrite
PolissacarÃdeos
Dor
Cartilagem
Gomas Vegetais
topic Osteoartrite
PolissacarÃdeos
Dor
Cartilagem
Gomas Vegetais
Osteoarthritis
Polysaccharides
Pain
Cartilage
Plant Gums
FARMACOLOGIA
dc.subject.eng.fl_str_mv Osteoarthritis
Polysaccharides
Pain
Cartilage
Plant Gums
dc.subject.cnpq.fl_str_mv FARMACOLOGIA
dc.description.sponsorship.fl_txt_mv CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
dc.description.abstract..fl_txt_mv 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 (200Âg i.art.) was given at day 4 only, 30 min before the pain evaluation. Naloxone (500Âg i. art.) was given 15 min prior morphine. Sodium alendronate (30 or 240Âg i. art.) was given prophilactically, starting 3 days prior ACLT, and repeated at each 3 days, until day 6. Original or chemically modified GG (100&#956;g/50&#956;l i. art.) was given as a single dose at day 4. Galactose or mannose was co-administred (500&#956;g/50&#956;l i. art.) with original GG. In the study of chondroprotection, GG (100&#956;g/50&#956;l 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
dc.description.abstract.por.fl_txt_mv No modelo de osteoartrite (OA) induzida por transecÃÃo do ligamento cruzado anterior em ratos (TLCA), havÃamos demonstrado que a goma guar (GG), uma galactomanana extraÃda das sementes de Cyamopsis tetragonolobus goma guar, apresenta atividade analgÃsica em magnitude semelhante à exibida pelo Hilano G-F 20, um derivado do Ãcido hialurÃnico utilizado em terapia intra-articular da OA humana. Utilizando o referido modelo, objetivamos desenvolver um mÃtido bioquÃmico paramÃtrico para avaliaÃÃo da lesÃo articular no referido modelo, e investigar o mecanismo para a analgesia e a eficÃcia condroprotetora da GG. Ratos Wistar submetidos à TLCA (grupo OA) foram sacrificados em diferentes perÃodos. A dor articular foi avaliada diariamente pelo teste de incapacitaÃÃo para ratos, por atà 70 dias. O lavado articular foi usado para determinaÃÃo da liberaÃÃo de NO. A cartilagem foi avaliada pela determinaÃÃo do teor de condrotin-sulfato (CS) na matriz, alÃm da avaliaÃÃo da massa molar do mesmo. A lesÃo articular foi avaliada tambÃm por anÃlise histopatolÃgica, segundo os escores OARSI. Grupos falso-operados (sham) foram utilizados para comparaÃÃo. 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 sÃtimo dias. Morfina (200Âg i. art.) foi administrada apenas no quarto dia, 30 min antes da avaliaÃÃo da dor. Naloxona (500Âg i. art.) foi administrada 15 min antes de morfina. Alendronato sÃdico (30 ou 240Âg/kg s.c.) foi administrado profilaticamente trÃs dias antes da induÃÃo, e repetido a cada trÃs dias, atà o sexto dia. GG original ou quimicamente modificada foi administrada em dose Ãnica no quarto dia (100&#956;g/50&#956;l i. art.). Galactose ou manose (500&#956;g/50&#956;l i. art.) foram co-administrados à GG original. Para avaliaÃÃo sobre a lesÃo da cartilagem, GG (100&#956;g/50&#956;l i. art) foi administrada como dose Ãnica semanal, do 14 ao 63 dias. Animais nÃo tratados (NT) receberam veÃculo (salina) nas respectivas vias. O grupo OA apresentou dor articular mÃxima durante a primeira semana, perÃodo no qual houve a maior liberaÃÃo de NO. 70 dias apÃs TLCA, o teor e a massa molar do CS da matriz da cartilagem mostraram-se ambos aumentados (p<0,05). Importantes alteraÃÃes histopatolÃgicas foram encontradas no grupo OA nesse perÃodo. Indometacina, meloxicam, tadalafila e morfina reduziram significantemente a dor (p<0,05), sendo o efeito desta Ãltima revertido por naloxona. Alendronato sÃdico preveniu a ocorrÃncia da dor. As estruturas modificadas de GG nÃo exibiram eficÃcia analgÃsica. Galactose, mas nÃo manose, reverteu significativamente o efeito analgÃsico da GG nÃo-modificada (p<0,01). GG preveniu as alteraÃÃes do CS da cartilagem, e reduziu significativamente a lesÃo histopatolÃgica (p<0,05). As alteraÃÃes sofridas pelo CS parecem refletir o dano tecidual, validando tal metodologia para avaliaÃÃo da lesÃo estrutural. A eficÃcia analgÃsica da GG decorre de um efeito farmacolÃgico dependente de galactose. Mais ainda, demonstramos a eficÃcia condroprotetora in vivo para a GG, indispendÃvel para sua validaÃÃo como droga anti-artrÃsica.
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 (200Âg i.art.) was given at day 4 only, 30 min before the pain evaluation. Naloxone (500Âg i. art.) was given 15 min prior morphine. Sodium alendronate (30 or 240Âg i. art.) was given prophilactically, starting 3 days prior ACLT, and repeated at each 3 days, until day 6. Original or chemically modified GG (100&#956;g/50&#956;l i. art.) was given as a single dose at day 4. Galactose or mannose was co-administred (500&#956;g/50&#956;l i. art.) with original GG. In the study of chondroprotection, GG (100&#956;g/50&#956;l 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.issued.fl_str_mv 2008-04-15
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