Envolvimento do receptor de potencial transitório de anquirina 1 na nocicepção e inflamação induzida pela radiação ultravioleta B em camundongos
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/21963 |
Resumo: | Burn injuries cause psychological and economically impacts since is characterized as debilitating and lifelong injuries causing dramatic clinical effects in humans. These injuries can be caused by several factors, chemicals substances, fire, scald, contacts with hot surfaces or ultraviolet (UV) radiation. Ultraviolet B (UVB) radiation exposure promotes sunburn and thus acute and chronic inflammatory processes contributing to pain development and maintenance. Sunburn pharmacological treatments currently available are used to alleviate the patients’ discomfort (pain and inflammation). However, these therapies are associated with adverse effects that limit their use. For this reason, it is relevant to identify new molecular targets to treat inflammatory pain conditions, including sunburn. A potential therapeutic target is the transient receptor potential ankyrin 1 (TRPA1), which is involved in a variety of inflammatory pain models. TRPA1 channel is activated by exogenous irritants compounds, extracellular Ca2+ influx and several endogenous oxidant molecules that are produced during tissue damage and inflammation, as by UV radiation. We evaluated the peripheral participation of TRPA1 using a topical treatment containing 0.05% HC030031 (a selective TRPA1 antagonist) on nociception and inflammation caused by a UVB radiation-induced burn model in male mice (25-30g), approved by Institutional Committee for Animal Care and Use-UFSM (protocol number 2479201217/2018). The mice were anesthetized and just the right hind paw was exposed to UVB radiation for 21 minutes (0.75 J/cm2). The topical treatments with different gels formulations (base gel, silver sulfadiazine 1%; positive control, HC030031 0.05%) were applied once a day for 8 days. Nociceptive (mechanical and cold allodynia and thermal hyperalgesia) and inflammatory (edema measurement) parameters were evaluated during 8 days always at 24h after topical treatment. The inflammatory cell infiltration was evaluated by myeloperoxidase (MPO) enzyme activity and histological analysis at 24h after UVB radiation. H2O2 levels (a TRPA1 agonist) in the irradiated paw tissue, and Ca2+ influx in mice spinal cord synaptosomes were determined to evaluate a possible mechanism of activation TRPA1 channel by UVB radiation. The gels formulations stability was also evaluated. The HC030031 0.05% reversed the mechanical and cold allodynia UVB-radiation induced with maximum inhibition (Imax) of 69±13% and 100% (4th day), respectively. HC030031 0.05% also reduced the paw edema and MPO activity with Imax of 77±6% on the 5th day and 69±28%, respectively. The reduced leukocyte infiltration was confirmed by histological analysis at the paw tissue. The UVB radiation increased the H2O2 levelsand the Ca2+ influx in mice spinal cord synaptosomes. The UVB radiation-induced Ca2+ influx was reduced by HC030031. HC030031 gel presented suitable pH and spreadability factor ensuring its quality and the therapeutic effect. Our results confirm the activation of the TRPA1 channel by UVB radiation, suggesting that topical TRPA1 antagonists can be a new strategy or therapy for the adjuvant treatment of the sunburn-associated pain and inflammation. |
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Envolvimento do receptor de potencial transitório de anquirina 1 na nocicepção e inflamação induzida pela radiação ultravioleta B em camundongosInvolvement of transient receptor potential ankyrin 1 in nociception and inflammation ultraviolet B radiation-induced in miceQueimadura-solarUVBHC030031AntinocicepçãoPeróxido de hidrogênioInfluxo de cálcioSunburnAntinociceptionHydrogen peroxideCalcium influxCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICABurn injuries cause psychological and economically impacts since is characterized as debilitating and lifelong injuries causing dramatic clinical effects in humans. These injuries can be caused by several factors, chemicals substances, fire, scald, contacts with hot surfaces or ultraviolet (UV) radiation. Ultraviolet B (UVB) radiation exposure promotes sunburn and thus acute and chronic inflammatory processes contributing to pain development and maintenance. Sunburn pharmacological treatments currently available are used to alleviate the patients’ discomfort (pain and inflammation). However, these therapies are associated with adverse effects that limit their use. For this reason, it is relevant to identify new molecular targets to treat inflammatory pain conditions, including sunburn. A potential therapeutic target is the transient receptor potential ankyrin 1 (TRPA1), which is involved in a variety of inflammatory pain models. TRPA1 channel is activated by exogenous irritants compounds, extracellular Ca2+ influx and several endogenous oxidant molecules that are produced during tissue damage and inflammation, as by UV radiation. We evaluated the peripheral participation of TRPA1 using a topical treatment containing 0.05% HC030031 (a selective TRPA1 antagonist) on nociception and inflammation caused by a UVB radiation-induced burn model in male mice (25-30g), approved by Institutional Committee for Animal Care and Use-UFSM (protocol number 2479201217/2018). The mice were anesthetized and just the right hind paw was exposed to UVB radiation for 21 minutes (0.75 J/cm2). The topical treatments with different gels formulations (base gel, silver sulfadiazine 1%; positive control, HC030031 0.05%) were applied once a day for 8 days. Nociceptive (mechanical and cold allodynia and thermal hyperalgesia) and inflammatory (edema measurement) parameters were evaluated during 8 days always at 24h after topical treatment. The inflammatory cell infiltration was evaluated by myeloperoxidase (MPO) enzyme activity and histological analysis at 24h after UVB radiation. H2O2 levels (a TRPA1 agonist) in the irradiated paw tissue, and Ca2+ influx in mice spinal cord synaptosomes were determined to evaluate a possible mechanism of activation TRPA1 channel by UVB radiation. The gels formulations stability was also evaluated. The HC030031 0.05% reversed the mechanical and cold allodynia UVB-radiation induced with maximum inhibition (Imax) of 69±13% and 100% (4th day), respectively. HC030031 0.05% also reduced the paw edema and MPO activity with Imax of 77±6% on the 5th day and 69±28%, respectively. The reduced leukocyte infiltration was confirmed by histological analysis at the paw tissue. The UVB radiation increased the H2O2 levelsand the Ca2+ influx in mice spinal cord synaptosomes. The UVB radiation-induced Ca2+ influx was reduced by HC030031. HC030031 gel presented suitable pH and spreadability factor ensuring its quality and the therapeutic effect. Our results confirm the activation of the TRPA1 channel by UVB radiation, suggesting that topical TRPA1 antagonists can be a new strategy or therapy for the adjuvant treatment of the sunburn-associated pain and inflammation.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESAs lesões por queimaduras causam impactos psicológicos e econômicos, uma vez que são caracterizadas por causar lesões debilitantes e ao longo da vida, proporcionam efeitos clínicos dramáticos. Essas lesões podem ser causadas por vários fatores, como substâncias químicas, fogo, escaldadura, contato com superfícies quentes ou radiação ultravioleta (UV). A exposição à radiação ultravioleta B (UVB) promove queimaduras solares e, portanto, processos inflamatórios agudos e crônicos que contribuem para o desenvolvimento e manutenção da dor. Os tratamentos farmacológicos contra queimaduras solares atualmente disponíveis são usados para aliviar o desconforto nos pacientes (dor e inflamação). No entanto, essas terapias estão associadas a efeitos adversos que limitam seu uso. Por esse motivo, é relevante identificar novos alvos moleculares para o tratamento de condições de dor inflamatória, incluindo as queimaduras solares. Um alvo terapêutico potencial é o receptor de potencial transitório do tipo anquirina 1 (TRPA1), o qual está envolvido em uma variedade de modelos de dor inflamatória. O canal TRPA1 é ativado por compostos irritantes exógenos, influxo de Ca2+ extracelular e várias moléculas oxidantes endógenas que são produzidas durante a lesão e a inflamação tecidual, como as induzidas por radiação UV. Com isso, avaliou-se a participação periférica do TRPA1 utilizando um tratamento tópico contendo HC030031 0,05% (um antagonista seletivo TRPA1) na nocicepção e inflamação causada por um modelo de queimadura induzida por radiação UVB em camundongos machos (25-30g) (aprovado pelo CEUA-UFSM sob o protocolo número 2479201217/2018). Os camundongos foram anestesiados e apenas a pata traseira direita foi exposta a radiação UVB durante 21 minutos (0,75 J/cm2). Os tratamentos tópicos com as diferentes formulações géis (gel base, sulfadiazina de prata 1%; controle positivo, HC030031 0,05%) foram aplicados uma vez ao dia durante 8 dias. Os parâmetros nociceptivos (alodinia mecânica e ao frio e hiperalgesia térmica) e inflamatórios (avaliação do edema de pata) foram avaliados durante os 8 dias sempre em 24 h após o tratamento tópico. A infiltração de células inflamatórias foi avaliada pela atividade da enzima mieloperoxidase (MPO) e por análise histológica em 24 h após a radiação UVB. Os níveis de H2O2 (um agonista TRPA1) no tecido plantar irradiado e o influxo de Ca2+ em sinaptossomas da medula espinhal de camundongos foram determinados para avaliar um possível mecanismo de ativação do canal TRPA1 pela radiação UVB. A estabilidade das formulações em gel também foi avaliada. O HC030031 0,05% reduziu a alodinia mecânica e ao frio induzida pela radiação UVB com inibição máxima (Imax) de 69 ± 13% e 100% (4º dia), respectivamente. O HC030031 0,05% também reduziu o edema de pata e a atividade da MPO com Imax 77 ± 6% no 5º dia e 69 ± 28%, respectivamente. A redução da infiltração leucocitária foi confirmada por análise histológica no tecido plantar. A radiação UVB aumentou os níveis de H2O2) e o influxo de Ca2+ nos sinaptossomas da medula espinhal de camundongos. O influxo de Ca2+ induzido pela radiação UVB foi reduzido pelo HC030031. O HC030031 gel apresentou pH e fator de espalhabilidade adequado, garantindo sua qualidade e efeito terapêutico. Nossos resultados confirmam a ativação do canal TRPA1 pela radiação UVB, sugerindo que antagonistas tópicos do TRPA1 podem ser uma nova estratégia para o tratamento ou terapia adjuvante da dor e inflamação associada à queimadura solar.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasOliveira, Sara Marchesan dehttp://lattes.cnpq.br/6574555059806902Segatto, Ana Lúcia AnversaWilhelm, Ethel AntunesFialho, Maria Fernanda Pessano2021-08-16T23:10:58Z2021-08-16T23:10:58Z2019-08-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/21963porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2021-08-17T06:00:54Zoai:repositorio.ufsm.br:1/21963Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-08-17T06:00:54Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Envolvimento do receptor de potencial transitório de anquirina 1 na nocicepção e inflamação induzida pela radiação ultravioleta B em camundongos Involvement of transient receptor potential ankyrin 1 in nociception and inflammation ultraviolet B radiation-induced in mice |
title |
Envolvimento do receptor de potencial transitório de anquirina 1 na nocicepção e inflamação induzida pela radiação ultravioleta B em camundongos |
spellingShingle |
Envolvimento do receptor de potencial transitório de anquirina 1 na nocicepção e inflamação induzida pela radiação ultravioleta B em camundongos Fialho, Maria Fernanda Pessano Queimadura-solar UVB HC030031 Antinocicepção Peróxido de hidrogênio Influxo de cálcio Sunburn Antinociception Hydrogen peroxide Calcium influx CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Envolvimento do receptor de potencial transitório de anquirina 1 na nocicepção e inflamação induzida pela radiação ultravioleta B em camundongos |
title_full |
Envolvimento do receptor de potencial transitório de anquirina 1 na nocicepção e inflamação induzida pela radiação ultravioleta B em camundongos |
title_fullStr |
Envolvimento do receptor de potencial transitório de anquirina 1 na nocicepção e inflamação induzida pela radiação ultravioleta B em camundongos |
title_full_unstemmed |
Envolvimento do receptor de potencial transitório de anquirina 1 na nocicepção e inflamação induzida pela radiação ultravioleta B em camundongos |
title_sort |
Envolvimento do receptor de potencial transitório de anquirina 1 na nocicepção e inflamação induzida pela radiação ultravioleta B em camundongos |
author |
Fialho, Maria Fernanda Pessano |
author_facet |
Fialho, Maria Fernanda Pessano |
author_role |
author |
dc.contributor.none.fl_str_mv |
Oliveira, Sara Marchesan de http://lattes.cnpq.br/6574555059806902 Segatto, Ana Lúcia Anversa Wilhelm, Ethel Antunes |
dc.contributor.author.fl_str_mv |
Fialho, Maria Fernanda Pessano |
dc.subject.por.fl_str_mv |
Queimadura-solar UVB HC030031 Antinocicepção Peróxido de hidrogênio Influxo de cálcio Sunburn Antinociception Hydrogen peroxide Calcium influx CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Queimadura-solar UVB HC030031 Antinocicepção Peróxido de hidrogênio Influxo de cálcio Sunburn Antinociception Hydrogen peroxide Calcium influx CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Burn injuries cause psychological and economically impacts since is characterized as debilitating and lifelong injuries causing dramatic clinical effects in humans. These injuries can be caused by several factors, chemicals substances, fire, scald, contacts with hot surfaces or ultraviolet (UV) radiation. Ultraviolet B (UVB) radiation exposure promotes sunburn and thus acute and chronic inflammatory processes contributing to pain development and maintenance. Sunburn pharmacological treatments currently available are used to alleviate the patients’ discomfort (pain and inflammation). However, these therapies are associated with adverse effects that limit their use. For this reason, it is relevant to identify new molecular targets to treat inflammatory pain conditions, including sunburn. A potential therapeutic target is the transient receptor potential ankyrin 1 (TRPA1), which is involved in a variety of inflammatory pain models. TRPA1 channel is activated by exogenous irritants compounds, extracellular Ca2+ influx and several endogenous oxidant molecules that are produced during tissue damage and inflammation, as by UV radiation. We evaluated the peripheral participation of TRPA1 using a topical treatment containing 0.05% HC030031 (a selective TRPA1 antagonist) on nociception and inflammation caused by a UVB radiation-induced burn model in male mice (25-30g), approved by Institutional Committee for Animal Care and Use-UFSM (protocol number 2479201217/2018). The mice were anesthetized and just the right hind paw was exposed to UVB radiation for 21 minutes (0.75 J/cm2). The topical treatments with different gels formulations (base gel, silver sulfadiazine 1%; positive control, HC030031 0.05%) were applied once a day for 8 days. Nociceptive (mechanical and cold allodynia and thermal hyperalgesia) and inflammatory (edema measurement) parameters were evaluated during 8 days always at 24h after topical treatment. The inflammatory cell infiltration was evaluated by myeloperoxidase (MPO) enzyme activity and histological analysis at 24h after UVB radiation. H2O2 levels (a TRPA1 agonist) in the irradiated paw tissue, and Ca2+ influx in mice spinal cord synaptosomes were determined to evaluate a possible mechanism of activation TRPA1 channel by UVB radiation. The gels formulations stability was also evaluated. The HC030031 0.05% reversed the mechanical and cold allodynia UVB-radiation induced with maximum inhibition (Imax) of 69±13% and 100% (4th day), respectively. HC030031 0.05% also reduced the paw edema and MPO activity with Imax of 77±6% on the 5th day and 69±28%, respectively. The reduced leukocyte infiltration was confirmed by histological analysis at the paw tissue. The UVB radiation increased the H2O2 levelsand the Ca2+ influx in mice spinal cord synaptosomes. The UVB radiation-induced Ca2+ influx was reduced by HC030031. HC030031 gel presented suitable pH and spreadability factor ensuring its quality and the therapeutic effect. Our results confirm the activation of the TRPA1 channel by UVB radiation, suggesting that topical TRPA1 antagonists can be a new strategy or therapy for the adjuvant treatment of the sunburn-associated pain and inflammation. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-08-09 2021-08-16T23:10:58Z 2021-08-16T23:10:58Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/21963 |
url |
http://repositorio.ufsm.br/handle/1/21963 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1805922069320302592 |