Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos

Detalhes bibliográficos
Autor(a) principal: Moreira, Lorena Alves
Data de Publicação: 2017
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFG
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/8747
Resumo: Introduction: Crotamine is a low molecular weight cationic polypeptide (4.8 kDa), isolated from rattlesnake venom. In the previous study the presence of this toxin in the snake venom Crotalus durissus collilineatus was responsible for anti-edematogenic activity, suggesting its anti-inflammatory properties. Pain and inflammation are present mechanisms in several pathologies, being important the search for new compounds candidates for effective drugs and with less adverse effects than those existing in the market for such treatments. Objective: To determine acute oral toxicity of crotamine isolated from snake venom C. d. collilineatus was evaluated and its effects in experimental models of pain and inflammation in mice was investigated. Methodology: To evaluate acute oral toxicity, the up and down procedure and hippocratic screening was performed. For the nociceptive and inflammation assays, acetic acid-induced abdominal writhing, formalin-induced pain, ear edema induced by croton oil and pleurisy induced by carrageenan were performed. Results and Discussion: Crotamine did not cause lethality or signs of intoxication in the dose range of 0.34 to 10.88 mg/kg. In the abdominal writhing test, treatments at doses of 0.08, 0.16 and 0.32 mg/kg p.o. reduced the number of writhings in relation to the control by 34, 57 and 74 %, respectively, showing a dose-dependent trend. In the formalin-induced pain test it was observed that crotamine (0.16 mg/kg p.o.) reduced reactivity to pain in the neurogenic phase in 44.8% and in the inflammatory phase in 59.7%, suggesting antinociceptive activity. In addition, crotamine (0.16 mg/kg p.o.) was able to reduce ear edema induced by croton oil by 77 %, showing antidematogenic activity and reduced in 52.3 % the number of total leukocytes in the pleurisy test, reducing both neutrophil and mononuclear cells migration, thus exhibiting antimigratory activity. Conclusion: Crotamine did not induce a toxic or lethal effect at the doses tested. The reductions in writhings, reactivity to pain, ear edema and leukocytes migration with administration of crotamine were significant, suggesting that it has antinociceptive and anti-inflammatory activities.
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spelling Cunha, Luiz Carlos dahttp://lattes.cnpq.br/6349547031976679Cunha, Luiz Carlos daFajemiroye, James OluwagbamigbeRodrigues, Caroline Regohttp://lattes.cnpq.br/2987551169330650Moreira, Lorena Alves2018-07-30T14:03:46Z2017-04-28MOREIRA, Lorena Alves. Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos. 2017. 74 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2017.http://repositorio.bc.ufg.br/tede/handle/tede/8747Introduction: Crotamine is a low molecular weight cationic polypeptide (4.8 kDa), isolated from rattlesnake venom. In the previous study the presence of this toxin in the snake venom Crotalus durissus collilineatus was responsible for anti-edematogenic activity, suggesting its anti-inflammatory properties. Pain and inflammation are present mechanisms in several pathologies, being important the search for new compounds candidates for effective drugs and with less adverse effects than those existing in the market for such treatments. Objective: To determine acute oral toxicity of crotamine isolated from snake venom C. d. collilineatus was evaluated and its effects in experimental models of pain and inflammation in mice was investigated. Methodology: To evaluate acute oral toxicity, the up and down procedure and hippocratic screening was performed. For the nociceptive and inflammation assays, acetic acid-induced abdominal writhing, formalin-induced pain, ear edema induced by croton oil and pleurisy induced by carrageenan were performed. Results and Discussion: Crotamine did not cause lethality or signs of intoxication in the dose range of 0.34 to 10.88 mg/kg. In the abdominal writhing test, treatments at doses of 0.08, 0.16 and 0.32 mg/kg p.o. reduced the number of writhings in relation to the control by 34, 57 and 74 %, respectively, showing a dose-dependent trend. In the formalin-induced pain test it was observed that crotamine (0.16 mg/kg p.o.) reduced reactivity to pain in the neurogenic phase in 44.8% and in the inflammatory phase in 59.7%, suggesting antinociceptive activity. In addition, crotamine (0.16 mg/kg p.o.) was able to reduce ear edema induced by croton oil by 77 %, showing antidematogenic activity and reduced in 52.3 % the number of total leukocytes in the pleurisy test, reducing both neutrophil and mononuclear cells migration, thus exhibiting antimigratory activity. Conclusion: Crotamine did not induce a toxic or lethal effect at the doses tested. The reductions in writhings, reactivity to pain, ear edema and leukocytes migration with administration of crotamine were significant, suggesting that it has antinociceptive and anti-inflammatory activities.Introdução: A crotamina é um polipeptídeo catiônico de baixo peso molecular (ca.4,8 kDa), extraído da peçonha das cascavéis. A presença desta toxina na peçonha de serpentes Crotalus durissus collilineatus foi responsável por apresentar atividade anti-edematogênica, sugerindo atividade anti-inflamatória da mesma. A dor e a inflamação são mecanismos presentes em diversas patologias, sendo importante a busca por novos compostos candidatos a fármacos eficazes e com menos efeitos adversos do que os existentes no mercado para tais tratamentos. Objetivo: Determinar a toxicidade aguda oral da crotamina isolada da peçonha de serpentes C. d. collilineatus e investigar seus efeitos em modelos experimentais de dor e inflamação em camundongos. Metodologia: Para avaliação da toxicidade aguda oral foi realizado o método up and down, de acordo com o Guia OECD 425 e a realização do screening hipocrático. Para os ensaios antinociceptivo e anti-inflamatório foram realizados testes de contorções abdominais induzidas por ácido acético, dor induzida por formalina, edema de orelha induzido por óleo de cróton e pleurisia induzida por carragenina. Resultados e Discussão: A crotamina não causou letalidade ou sinais de intoxicação na faixa de dose de 0,34 a 10,88 mg/kg. No teste de contorções abdominais, os tratamentos com as doses de 0,08, 0,16 e 0,32 mg/kg p.o. reduziram em 34, 57 e 74 %, respectivamente, o número de contorções em relação ao controle, apresentando tendência dose-dependente. Com o teste de dor induzida por formalina, observou-se que a crotamina (0,16 mg/kg p.o.) reduziu a reatividade à dor na fase neurogênica em 44,8 % e, na fase inflamatória, em 59,7 %, sugerindo uma atividade antinociceptiva. Além disso, a crotamina (0,16 mg/kg p.o.) foi capaz de reduzir em 77 % o edema de orelha induzido por óleo de cróton, apresentando atividade anti-edematogênica e reduziu em 52,3 % o número de leucócitos totais no teste de pleurisia, reduzindo a migração de neutrófilos e células mononucleares, exibindo assim actividade antimigratória. Conclusões: A crotamina não induziu efeito tóxico ou letal nas doses testadas. As reduções no número das contorções, na reatividade à dor, no edema de orelha e na migração de leucócitos, com administração da crotamina foram significativas, sugerindo que a mesma apresente atividades antinociceptiva e anti-inflamatória.Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2018-07-27T16:43:08Z No. of bitstreams: 2 Dissertação - Lorena Alves Moreira - 2017.pdf: 1637184 bytes, checksum: f22c13c5c8bfa0acda4db5c61b821da1 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-07-30T14:03:46Z (GMT) No. of bitstreams: 2 Dissertação - Lorena Alves Moreira - 2017.pdf: 1637184 bytes, checksum: f22c13c5c8bfa0acda4db5c61b821da1 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2018-07-30T14:03:46Z (GMT). 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dc.title.eng.fl_str_mv Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos
dc.title.alternative.eng.fl_str_mv Evaluation of acute oral toxicity, antinociceptive and antiinflammatory activities of the isolated crotamine of Crotalus durissus collilineatus venom on mice
title Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos
spellingShingle Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos
Moreira, Lorena Alves
Crotalus durissus collilineatus
Crotamina
Analgesia
Inflamação
Toxicidade
Crotamine
Antinociceptive effect
Inflammation
Toxicity
CIENCIAS DA SAUDE::FARMACIA
title_short Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos
title_full Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos
title_fullStr Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos
title_full_unstemmed Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos
title_sort Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos
author Moreira, Lorena Alves
author_facet Moreira, Lorena Alves
author_role author
dc.contributor.advisor1.fl_str_mv Cunha, Luiz Carlos da
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/6349547031976679
dc.contributor.referee1.fl_str_mv Cunha, Luiz Carlos da
dc.contributor.referee2.fl_str_mv Fajemiroye, James Oluwagbamigbe
dc.contributor.referee3.fl_str_mv Rodrigues, Caroline Rego
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/2987551169330650
dc.contributor.author.fl_str_mv Moreira, Lorena Alves
contributor_str_mv Cunha, Luiz Carlos da
Cunha, Luiz Carlos da
Fajemiroye, James Oluwagbamigbe
Rodrigues, Caroline Rego
dc.subject.por.fl_str_mv Crotalus durissus collilineatus
Crotamina
Analgesia
Inflamação
Toxicidade
topic Crotalus durissus collilineatus
Crotamina
Analgesia
Inflamação
Toxicidade
Crotamine
Antinociceptive effect
Inflammation
Toxicity
CIENCIAS DA SAUDE::FARMACIA
dc.subject.eng.fl_str_mv Crotamine
Antinociceptive effect
Inflammation
Toxicity
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::FARMACIA
description Introduction: Crotamine is a low molecular weight cationic polypeptide (4.8 kDa), isolated from rattlesnake venom. In the previous study the presence of this toxin in the snake venom Crotalus durissus collilineatus was responsible for anti-edematogenic activity, suggesting its anti-inflammatory properties. Pain and inflammation are present mechanisms in several pathologies, being important the search for new compounds candidates for effective drugs and with less adverse effects than those existing in the market for such treatments. Objective: To determine acute oral toxicity of crotamine isolated from snake venom C. d. collilineatus was evaluated and its effects in experimental models of pain and inflammation in mice was investigated. Methodology: To evaluate acute oral toxicity, the up and down procedure and hippocratic screening was performed. For the nociceptive and inflammation assays, acetic acid-induced abdominal writhing, formalin-induced pain, ear edema induced by croton oil and pleurisy induced by carrageenan were performed. Results and Discussion: Crotamine did not cause lethality or signs of intoxication in the dose range of 0.34 to 10.88 mg/kg. In the abdominal writhing test, treatments at doses of 0.08, 0.16 and 0.32 mg/kg p.o. reduced the number of writhings in relation to the control by 34, 57 and 74 %, respectively, showing a dose-dependent trend. In the formalin-induced pain test it was observed that crotamine (0.16 mg/kg p.o.) reduced reactivity to pain in the neurogenic phase in 44.8% and in the inflammatory phase in 59.7%, suggesting antinociceptive activity. In addition, crotamine (0.16 mg/kg p.o.) was able to reduce ear edema induced by croton oil by 77 %, showing antidematogenic activity and reduced in 52.3 % the number of total leukocytes in the pleurisy test, reducing both neutrophil and mononuclear cells migration, thus exhibiting antimigratory activity. Conclusion: Crotamine did not induce a toxic or lethal effect at the doses tested. The reductions in writhings, reactivity to pain, ear edema and leukocytes migration with administration of crotamine were significant, suggesting that it has antinociceptive and anti-inflammatory activities.
publishDate 2017
dc.date.issued.fl_str_mv 2017-04-28
dc.date.accessioned.fl_str_mv 2018-07-30T14:03:46Z
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dc.identifier.citation.fl_str_mv MOREIRA, Lorena Alves. Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos. 2017. 74 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2017.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/8747
identifier_str_mv MOREIRA, Lorena Alves. Avaliação da toxicidade aguda oral, atividades antinociceptiva e anti-inflamatória da crotamina isolada da peçonha de Crotalus durissus collilineatus em camundongos. 2017. 74 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2017.
url http://repositorio.bc.ufg.br/tede/handle/tede/8747
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dc.publisher.none.fl_str_mv Universidade Federal de Goiás
dc.publisher.program.fl_str_mv Programa de Pós-graduação em Ciências Farmacêuticas (FF)
dc.publisher.initials.fl_str_mv UFG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Faculdade Farmácia - FF (RG)
publisher.none.fl_str_mv Universidade Federal de Goiás
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institution UFG
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http://repositorio.bc.ufg.br/tede/bitstreams/a7e407eb-cd21-464c-9b49-27c21ec1e27e/download
http://repositorio.bc.ufg.br/tede/bitstreams/ea7f3520-1f7d-43fa-bb91-a17f82eab0a1/download
bitstream.checksum.fl_str_mv bd3efa91386c1718a7f26a329fdcb468
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bitstream.checksumAlgorithm.fl_str_mv MD5
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repository.name.fl_str_mv Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)
repository.mail.fl_str_mv tasesdissertacoes.bc@ufg.br
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