Protein fraction of latex Calotropis procera protects against induced oral mucositis 5-Fluorouracil in hamsters through inhibition proinflammatory mediators

Detalhes bibliográficos
Autor(a) principal: Ana Paula Fragoso de Freitas
Data de Publicação: 2011
Tipo de documento: Dissertação
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=9245
Resumo: Oral mucositis (OM) induced by antineoplasic drugs is an important, dose-limiting, and costly side effect of cancer therapy. Calotropis procera is a plant plant constitutively produces abundant latex that is reported to possess anti-inflammatory, bacteriolytic, insecticidal, analgesic properties. The present work aimed to describe the effect of laticifer proteins of Calotropis procera (LP) in the expression of pro-inflammatory cytokines and inducible enzymes, such as, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the model of OM in Hamsters. OM was induced by two intraperitoneal (i.p.) administrations of 5-Fluorouracil (5-FU) on the 1st and 2nd days (60 and 40 mg/kg, respectively) in hamsters (n=5). LP (0,25; 1; 5 E 25 mg / kg) was injected i.p. 24h before and 24h after mechanical trauma of the cheek pouches. Control group received only saline. On the 10th day, the animals were sacrificed and tissues from the cheek pouches were harvested. Macroscopical and histopathological (inflammatory cell infiltration, edema, hemorrhage and the formation of ulcerations and abscess) analysis as well as immunohistochemistry for TNF-&#61537;, IL-1&#946;, iNOS and COX-2 was performed in the cheek pouch tissue. Kruskal Wallis/Dunn was used as statistical tests. P<0.05 was accepted. Ethics Committee 036/10. The LP significantly inhibited macroscopical and histopathological parameters when compared to control group with maximum effect in macroscopic scores reaching 75% and 66% of maximum effect at the histopathological evaluation. The MPO activity was also significantly inhibited by LP in 91% at the same dose (p<0,001) and also inhibited the lost weight of 5- FU induced-oral mucositis. The cheek pouches of hamsters submitted to OM showed marked immunostaining for TNF-&#61537;, IL-1&#946;, iNOS and COX-2 on inflamed conjunctive (Cj) and epithelial (Ep) tissue compared with the cheek pouches of the normal control group. LP caused considerable reduction in the immunostaining for TNF-&#61537; (62%,Cj; 70%,Ep), IL-1&#946; (87%,Cj; 80%,Ep), iNOS (82%Cj; 52%Ep) and COX-2 (70%,Cj; 100%,Ep) in the check pouches tissue when compared with the group of animals subjected to experimental mucositis that received saline instead of LP. These findings show anti-inflammatory effects of LP in 5-FU-induced OM. The protective effect could be supported by the reduction of the expression of pro-inflammatory cytokines, such as TNF-&#61537; and IL-1&#946; and the enzymes iNOS and COX-2. The protective mechanism appears to involve inhibition of the expression of iNOS, COX-2, TNF-&#61537;, and IL- 1&#946;.
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spelling info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisProtein fraction of latex Calotropis procera protects against induced oral mucositis 5-Fluorouracil in hamsters through inhibition proinflammatory mediatorsFraÃÃo protÃica do lÃtex da Calotropis procera protege contra a mucosite oral induzida por 5-Fluorouracil em hamsters atravÃs da inibiÃÃo de mediadores prÃ-inflamatÃrios2011-12-07Mariana Lima Vale69461538391http://lattes.cnpq.br/2233181081815735Nylane Maria Nunes de Alencar32184573353http://lattes.cnpq.br/9219662256316695Adriana Rolim Campos Barros73902500387http://lattes.cnpq.br/3791336333658295 96917199320http://lattes.cnpq.br/0812207648004712Ana Paula Fragoso de FreitasUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em CiÃncias MÃdicasUFCBRFraÃÃo protÃicaOral Mucositis 5-Fluorouracil Calotropis procera latex protein fraction inflammation cancer chemotherapyCIENCIAS DA SAUDEOral mucositis (OM) induced by antineoplasic drugs is an important, dose-limiting, and costly side effect of cancer therapy. Calotropis procera is a plant plant constitutively produces abundant latex that is reported to possess anti-inflammatory, bacteriolytic, insecticidal, analgesic properties. The present work aimed to describe the effect of laticifer proteins of Calotropis procera (LP) in the expression of pro-inflammatory cytokines and inducible enzymes, such as, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the model of OM in Hamsters. OM was induced by two intraperitoneal (i.p.) administrations of 5-Fluorouracil (5-FU) on the 1st and 2nd days (60 and 40 mg/kg, respectively) in hamsters (n=5). LP (0,25; 1; 5 E 25 mg / kg) was injected i.p. 24h before and 24h after mechanical trauma of the cheek pouches. Control group received only saline. On the 10th day, the animals were sacrificed and tissues from the cheek pouches were harvested. Macroscopical and histopathological (inflammatory cell infiltration, edema, hemorrhage and the formation of ulcerations and abscess) analysis as well as immunohistochemistry for TNF-&#61537;, IL-1&#946;, iNOS and COX-2 was performed in the cheek pouch tissue. Kruskal Wallis/Dunn was used as statistical tests. P<0.05 was accepted. Ethics Committee 036/10. The LP significantly inhibited macroscopical and histopathological parameters when compared to control group with maximum effect in macroscopic scores reaching 75% and 66% of maximum effect at the histopathological evaluation. The MPO activity was also significantly inhibited by LP in 91% at the same dose (p<0,001) and also inhibited the lost weight of 5- FU induced-oral mucositis. The cheek pouches of hamsters submitted to OM showed marked immunostaining for TNF-&#61537;, IL-1&#946;, iNOS and COX-2 on inflamed conjunctive (Cj) and epithelial (Ep) tissue compared with the cheek pouches of the normal control group. LP caused considerable reduction in the immunostaining for TNF-&#61537; (62%,Cj; 70%,Ep), IL-1&#946; (87%,Cj; 80%,Ep), iNOS (82%Cj; 52%Ep) and COX-2 (70%,Cj; 100%,Ep) in the check pouches tissue when compared with the group of animals subjected to experimental mucositis that received saline instead of LP. These findings show anti-inflammatory effects of LP in 5-FU-induced OM. The protective effect could be supported by the reduction of the expression of pro-inflammatory cytokines, such as TNF-&#61537; and IL-1&#946; and the enzymes iNOS and COX-2. The protective mechanism appears to involve inhibition of the expression of iNOS, COX-2, TNF-&#61537;, and IL- 1&#946;.Mucosite oral (MO) induzida por drogas antineoplÃsicas à um importante fator limitante da dose e efeitos colaterais da terapia do cÃncer. Calotropis procera à uma planta que produz lÃtex constitutivamente abundante que à relatado possuir propriedades antiinflamatÃrias, bactericidas, inseticidas, analgÃsicas. O presente trabalho teve como objetivo descrever o efeito das proteÃnas do lÃtex da Calotropis procera (LP) na expressÃo de citocinas prÃ-inflamatÃrias (TNF-&#945; e IL-1&#61538;) e enzimas induzÃveis, como, ciclooxigenase-2 (COX-2) e Ãxido nÃtrico sintase induzÃvel (NOSi) no modelo de MO em hamsters. A mucosite oral foi induzida por duas administraÃÃes intraperitoneal (i.p) de 5-fluorouracil (5-FU) no 1  e 2 dias nas doses de 60 e 40 mg/kg, respectivamente nos animais (n = 5). As LP (0,25; 1; 5 E 25 mg/kg) foi injetado via i.p. 24h antes e 24h apÃs o trauma mecÃnico da mucosa jugal. O grupo controle recebeu apenas soluÃÃo salina. No 10 dia, os animais foram sacrificados e os tecidos da mucosa jugal foram colhidos. Foram realizadas no tecido mucosa jugal as anÃlises macroscÃpicas e histopatolÃgicas (infiltraÃÃo de cÃlulas inflamatÃrias, edema, hemorragia e à formaÃÃo de ulceraÃÃes e abscessos), bem como a imunohistoquÃmica para TNF-&#945;, IL-1&#946;, NOSi e COX-2. Foram utilizados Kruskal Wallis / Dunn como testes estatÃsticos, onde P <0,05 foi aceito. O estudo foi submetido ao Comità de Ãtica sob o protocolo 036/10. Observou-se que a LP inibiu significativamente parÃmetros macroscÃpicos e histopatolÃgicos, quando comparado ao grupo controle, com efeito mÃximo nos escores macroscÃpicos atingindo 75% e 66% do efeito mÃximo na avaliaÃÃo histopatolÃgica. A atividade de Mieloperoxidase (MPO) tambÃm foi significativamente inibida por LP em 91% com a mesma dose (p <0,001) quando comparado ao grupo controle e tambÃm inibiu a perda de peso em animais submetidos a mucosite oral e tratados com LP. A mucosa jugal dos animais submetidos a MO mostrou imunomarcaÃÃo para TNF-&#945;, IL-1&#946;, NOSi e COX-2 na conjuntiva inflamada (Cj) e tecido epitelial (Ep) em comparaÃÃo com o tecido jugal do grupo normal. LP causou reduÃÃo considerÃvel na imunomarcaÃÃo para TNF-&#945; (62%, Cj, 70%, Ep), IL-1&#946; (87%, Cj, 80%, Ep), NOSi (82% Cj; Ep 52%) e COX -2 (70%, Cj, 100%, Ep) no tecido jugal quando comparado com o grupo de animais submetidos à mucosite experimental que receberam salina, em vez de LP. Esses achados demonstram efeitos anti-inflamatÃrios de LP em MO induzida por 5-FU. O efeito protetor poderia ser suportado pela reduÃÃo da expressÃo das citocinas prÃ-inflamatÃrias, como TNF-&#945; e IL-1&#946; e na expressÃo de enzimas COX-2 e NOSi. O mecanismo de proteÃÃo parece envolver a expressÃo inibitÃria da NOSi, COX-2, TNF-&#945; e IL-1&#946;.CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorCoordenaÃÃo de AperfeiÃoamento de NÃvel Superiorhttp://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=9245application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:22:32Zmail@mail.com -
dc.title.en.fl_str_mv Protein fraction of latex Calotropis procera protects against induced oral mucositis 5-Fluorouracil in hamsters through inhibition proinflammatory mediators
dc.title.alternative.pt.fl_str_mv FraÃÃo protÃica do lÃtex da Calotropis procera protege contra a mucosite oral induzida por 5-Fluorouracil em hamsters atravÃs da inibiÃÃo de mediadores prÃ-inflamatÃrios
title Protein fraction of latex Calotropis procera protects against induced oral mucositis 5-Fluorouracil in hamsters through inhibition proinflammatory mediators
spellingShingle Protein fraction of latex Calotropis procera protects against induced oral mucositis 5-Fluorouracil in hamsters through inhibition proinflammatory mediators
Ana Paula Fragoso de Freitas
FraÃÃo protÃica
Oral Mucositis
5-Fluorouracil
Calotropis procera
latex
protein fraction
inflammation
cancer chemotherapy
CIENCIAS DA SAUDE
title_short Protein fraction of latex Calotropis procera protects against induced oral mucositis 5-Fluorouracil in hamsters through inhibition proinflammatory mediators
title_full Protein fraction of latex Calotropis procera protects against induced oral mucositis 5-Fluorouracil in hamsters through inhibition proinflammatory mediators
title_fullStr Protein fraction of latex Calotropis procera protects against induced oral mucositis 5-Fluorouracil in hamsters through inhibition proinflammatory mediators
title_full_unstemmed Protein fraction of latex Calotropis procera protects against induced oral mucositis 5-Fluorouracil in hamsters through inhibition proinflammatory mediators
title_sort Protein fraction of latex Calotropis procera protects against induced oral mucositis 5-Fluorouracil in hamsters through inhibition proinflammatory mediators
author Ana Paula Fragoso de Freitas
author_facet Ana Paula Fragoso de Freitas
author_role author
dc.contributor.advisor1.fl_str_mv Mariana Lima Vale
dc.contributor.advisor1ID.fl_str_mv 69461538391
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2233181081815735
dc.contributor.referee1.fl_str_mv Nylane Maria Nunes de Alencar
dc.contributor.referee1ID.fl_str_mv 32184573353
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/9219662256316695
dc.contributor.referee2.fl_str_mv Adriana Rolim Campos Barros
dc.contributor.referee2ID.fl_str_mv 73902500387
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/3791336333658295
dc.contributor.authorID.fl_str_mv 96917199320
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0812207648004712
dc.contributor.author.fl_str_mv Ana Paula Fragoso de Freitas
contributor_str_mv Mariana Lima Vale
Nylane Maria Nunes de Alencar
Adriana Rolim Campos Barros
dc.subject.por.fl_str_mv FraÃÃo protÃica
topic FraÃÃo protÃica
Oral Mucositis
5-Fluorouracil
Calotropis procera
latex
protein fraction
inflammation
cancer chemotherapy
CIENCIAS DA SAUDE
dc.subject.eng.fl_str_mv Oral Mucositis
5-Fluorouracil
Calotropis procera
latex
protein fraction
inflammation
cancer chemotherapy
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE
dc.description.sponsorship.fl_txt_mv CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior
dc.description.abstract.por.fl_txt_mv Oral mucositis (OM) induced by antineoplasic drugs is an important, dose-limiting, and costly side effect of cancer therapy. Calotropis procera is a plant plant constitutively produces abundant latex that is reported to possess anti-inflammatory, bacteriolytic, insecticidal, analgesic properties. The present work aimed to describe the effect of laticifer proteins of Calotropis procera (LP) in the expression of pro-inflammatory cytokines and inducible enzymes, such as, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the model of OM in Hamsters. OM was induced by two intraperitoneal (i.p.) administrations of 5-Fluorouracil (5-FU) on the 1st and 2nd days (60 and 40 mg/kg, respectively) in hamsters (n=5). LP (0,25; 1; 5 E 25 mg / kg) was injected i.p. 24h before and 24h after mechanical trauma of the cheek pouches. Control group received only saline. On the 10th day, the animals were sacrificed and tissues from the cheek pouches were harvested. Macroscopical and histopathological (inflammatory cell infiltration, edema, hemorrhage and the formation of ulcerations and abscess) analysis as well as immunohistochemistry for TNF-&#61537;, IL-1&#946;, iNOS and COX-2 was performed in the cheek pouch tissue. Kruskal Wallis/Dunn was used as statistical tests. P<0.05 was accepted. Ethics Committee 036/10. The LP significantly inhibited macroscopical and histopathological parameters when compared to control group with maximum effect in macroscopic scores reaching 75% and 66% of maximum effect at the histopathological evaluation. The MPO activity was also significantly inhibited by LP in 91% at the same dose (p<0,001) and also inhibited the lost weight of 5- FU induced-oral mucositis. The cheek pouches of hamsters submitted to OM showed marked immunostaining for TNF-&#61537;, IL-1&#946;, iNOS and COX-2 on inflamed conjunctive (Cj) and epithelial (Ep) tissue compared with the cheek pouches of the normal control group. LP caused considerable reduction in the immunostaining for TNF-&#61537; (62%,Cj; 70%,Ep), IL-1&#946; (87%,Cj; 80%,Ep), iNOS (82%Cj; 52%Ep) and COX-2 (70%,Cj; 100%,Ep) in the check pouches tissue when compared with the group of animals subjected to experimental mucositis that received saline instead of LP. These findings show anti-inflammatory effects of LP in 5-FU-induced OM. The protective effect could be supported by the reduction of the expression of pro-inflammatory cytokines, such as TNF-&#61537; and IL-1&#946; and the enzymes iNOS and COX-2. The protective mechanism appears to involve inhibition of the expression of iNOS, COX-2, TNF-&#61537;, and IL- 1&#946;.
Mucosite oral (MO) induzida por drogas antineoplÃsicas à um importante fator limitante da dose e efeitos colaterais da terapia do cÃncer. Calotropis procera à uma planta que produz lÃtex constitutivamente abundante que à relatado possuir propriedades antiinflamatÃrias, bactericidas, inseticidas, analgÃsicas. O presente trabalho teve como objetivo descrever o efeito das proteÃnas do lÃtex da Calotropis procera (LP) na expressÃo de citocinas prÃ-inflamatÃrias (TNF-&#945; e IL-1&#61538;) e enzimas induzÃveis, como, ciclooxigenase-2 (COX-2) e Ãxido nÃtrico sintase induzÃvel (NOSi) no modelo de MO em hamsters. A mucosite oral foi induzida por duas administraÃÃes intraperitoneal (i.p) de 5-fluorouracil (5-FU) no 1  e 2 dias nas doses de 60 e 40 mg/kg, respectivamente nos animais (n = 5). As LP (0,25; 1; 5 E 25 mg/kg) foi injetado via i.p. 24h antes e 24h apÃs o trauma mecÃnico da mucosa jugal. O grupo controle recebeu apenas soluÃÃo salina. No 10 dia, os animais foram sacrificados e os tecidos da mucosa jugal foram colhidos. Foram realizadas no tecido mucosa jugal as anÃlises macroscÃpicas e histopatolÃgicas (infiltraÃÃo de cÃlulas inflamatÃrias, edema, hemorragia e à formaÃÃo de ulceraÃÃes e abscessos), bem como a imunohistoquÃmica para TNF-&#945;, IL-1&#946;, NOSi e COX-2. Foram utilizados Kruskal Wallis / Dunn como testes estatÃsticos, onde P <0,05 foi aceito. O estudo foi submetido ao Comità de Ãtica sob o protocolo 036/10. Observou-se que a LP inibiu significativamente parÃmetros macroscÃpicos e histopatolÃgicos, quando comparado ao grupo controle, com efeito mÃximo nos escores macroscÃpicos atingindo 75% e 66% do efeito mÃximo na avaliaÃÃo histopatolÃgica. A atividade de Mieloperoxidase (MPO) tambÃm foi significativamente inibida por LP em 91% com a mesma dose (p <0,001) quando comparado ao grupo controle e tambÃm inibiu a perda de peso em animais submetidos a mucosite oral e tratados com LP. A mucosa jugal dos animais submetidos a MO mostrou imunomarcaÃÃo para TNF-&#945;, IL-1&#946;, NOSi e COX-2 na conjuntiva inflamada (Cj) e tecido epitelial (Ep) em comparaÃÃo com o tecido jugal do grupo normal. LP causou reduÃÃo considerÃvel na imunomarcaÃÃo para TNF-&#945; (62%, Cj, 70%, Ep), IL-1&#946; (87%, Cj, 80%, Ep), NOSi (82% Cj; Ep 52%) e COX -2 (70%, Cj, 100%, Ep) no tecido jugal quando comparado com o grupo de animais submetidos à mucosite experimental que receberam salina, em vez de LP. Esses achados demonstram efeitos anti-inflamatÃrios de LP em MO induzida por 5-FU. O efeito protetor poderia ser suportado pela reduÃÃo da expressÃo das citocinas prÃ-inflamatÃrias, como TNF-&#945; e IL-1&#946; e na expressÃo de enzimas COX-2 e NOSi. O mecanismo de proteÃÃo parece envolver a expressÃo inibitÃria da NOSi, COX-2, TNF-&#945; e IL-1&#946;.
description Oral mucositis (OM) induced by antineoplasic drugs is an important, dose-limiting, and costly side effect of cancer therapy. Calotropis procera is a plant plant constitutively produces abundant latex that is reported to possess anti-inflammatory, bacteriolytic, insecticidal, analgesic properties. The present work aimed to describe the effect of laticifer proteins of Calotropis procera (LP) in the expression of pro-inflammatory cytokines and inducible enzymes, such as, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the model of OM in Hamsters. OM was induced by two intraperitoneal (i.p.) administrations of 5-Fluorouracil (5-FU) on the 1st and 2nd days (60 and 40 mg/kg, respectively) in hamsters (n=5). LP (0,25; 1; 5 E 25 mg / kg) was injected i.p. 24h before and 24h after mechanical trauma of the cheek pouches. Control group received only saline. On the 10th day, the animals were sacrificed and tissues from the cheek pouches were harvested. Macroscopical and histopathological (inflammatory cell infiltration, edema, hemorrhage and the formation of ulcerations and abscess) analysis as well as immunohistochemistry for TNF-&#61537;, IL-1&#946;, iNOS and COX-2 was performed in the cheek pouch tissue. Kruskal Wallis/Dunn was used as statistical tests. P<0.05 was accepted. Ethics Committee 036/10. The LP significantly inhibited macroscopical and histopathological parameters when compared to control group with maximum effect in macroscopic scores reaching 75% and 66% of maximum effect at the histopathological evaluation. The MPO activity was also significantly inhibited by LP in 91% at the same dose (p<0,001) and also inhibited the lost weight of 5- FU induced-oral mucositis. The cheek pouches of hamsters submitted to OM showed marked immunostaining for TNF-&#61537;, IL-1&#946;, iNOS and COX-2 on inflamed conjunctive (Cj) and epithelial (Ep) tissue compared with the cheek pouches of the normal control group. LP caused considerable reduction in the immunostaining for TNF-&#61537; (62%,Cj; 70%,Ep), IL-1&#946; (87%,Cj; 80%,Ep), iNOS (82%Cj; 52%Ep) and COX-2 (70%,Cj; 100%,Ep) in the check pouches tissue when compared with the group of animals subjected to experimental mucositis that received saline instead of LP. These findings show anti-inflammatory effects of LP in 5-FU-induced OM. The protective effect could be supported by the reduction of the expression of pro-inflammatory cytokines, such as TNF-&#61537; and IL-1&#946; and the enzymes iNOS and COX-2. The protective mechanism appears to involve inhibition of the expression of iNOS, COX-2, TNF-&#61537;, and IL- 1&#946;.
publishDate 2011
dc.date.issued.fl_str_mv 2011-12-07
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
status_str publishedVersion
format masterThesis
dc.identifier.uri.fl_str_mv http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=9245
url http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=9245
dc.language.iso.fl_str_mv por
language por
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 Universidade Federal do CearÃ
dc.publisher.program.fl_str_mv Programa de PÃs-GraduaÃÃo em CiÃncias MÃdicas
dc.publisher.initials.fl_str_mv UFC
dc.publisher.country.fl_str_mv BR
publisher.none.fl_str_mv Universidade Federal do CearÃ
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFC
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instname_str Universidade Federal do Ceará
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