Avaliação da toxicidade pré-clínica de compostos iodado e mesilado, análogos ao metronidazol
| Ano de defesa: | 2007 |
|---|---|
| Autor(a) principal: | |
| Orientador(a): | |
| Banca de defesa: | |
| Tipo de documento: | Dissertação |
| Tipo de acesso: | Acesso aberto |
| Idioma: | por |
| Instituição de defesa: |
Universidade Federal de Minas Gerais
|
| Programa de Pós-Graduação: |
Não Informado pela instituição
|
| Departamento: |
Não Informado pela instituição
|
| País: |
Não Informado pela instituição
|
| Palavras-chave em Português: | |
| Link de acesso: | https://hdl.handle.net/1843/NCFA-7AKL85 |
Resumo: | Metronidazole (MTZ) is an antibacterial and antiprotozoal drug used in the treatment of several infections, included those caused by Helicobacter pylori. The present study aimed to evaluate the safety of two MTZ analogues, methanosulfonate (MTZ-Ms) and iodine (MTZI),that showed significant antibacterial activity even to MTZ-resistant strains, in rats through acute and subacute preclinical toxicity. In acute toxicity, 2000 mg/kg of MTZ-Ms was administered and no death was observed. 300 and 2000 mg/kg doses of MTZ-I were administered and one death was observed. In subacute toxicity, no abnormal behavior wasobserved with MTZ and MTZ-Ms. In the group treated with MTZ-I, it was detected a reduction in the weight gain and two death. The biochemical parameters evaluated showed a significant difference without a clinical correlation. Lymphocytes, leukocytes and red blood cells increased in the groups treated with MTZ and MTZ-Ms. Apoptose was observed in thePeyers patches and spleen. In histophatological examination it was observed hyperplasia of Peyers patches and degeneration of the testis and ovary in the groups treated with MTZ and MTZ-Ms. In conclusion, the raise of lymphocytes and Peyers patches suggest imunostimmulation action; MTZ-I presented a low degree of safety, the study suggests thatfurther investigations are needed for MTZ-Ms since it presents a greater degree of safety. |
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2019-08-11T11:18:35Z2025-09-08T22:50:45Z2019-08-11T11:18:35Z2007-03-16https://hdl.handle.net/1843/NCFA-7AKL85Metronidazole (MTZ) is an antibacterial and antiprotozoal drug used in the treatment of several infections, included those caused by Helicobacter pylori. The present study aimed to evaluate the safety of two MTZ analogues, methanosulfonate (MTZ-Ms) and iodine (MTZI),that showed significant antibacterial activity even to MTZ-resistant strains, in rats through acute and subacute preclinical toxicity. In acute toxicity, 2000 mg/kg of MTZ-Ms was administered and no death was observed. 300 and 2000 mg/kg doses of MTZ-I were administered and one death was observed. In subacute toxicity, no abnormal behavior wasobserved with MTZ and MTZ-Ms. In the group treated with MTZ-I, it was detected a reduction in the weight gain and two death. The biochemical parameters evaluated showed a significant difference without a clinical correlation. Lymphocytes, leukocytes and red blood cells increased in the groups treated with MTZ and MTZ-Ms. Apoptose was observed in thePeyers patches and spleen. In histophatological examination it was observed hyperplasia of Peyers patches and degeneration of the testis and ovary in the groups treated with MTZ and MTZ-Ms. In conclusion, the raise of lymphocytes and Peyers patches suggest imunostimmulation action; MTZ-I presented a low degree of safety, the study suggests thatfurther investigations are needed for MTZ-Ms since it presents a greater degree of safety.Universidade Federal de Minas Geraistoxicidade sub agudaMetronidazolanálogostoxicidade agudaImunoestimulaçãoToxicidade TestesMedicamentos Efeitos colateraisAgentes antibacterianosDrogas ToxicologiaToxicologiaFarmáciaAvaliação da toxicidade pré-clínica de compostos iodado e mesilado, análogos ao metronidazolinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisCarla Bonanato de Avelarinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGCarlos Alberto TagliatiMaria das Gracas CarvalhoSilvia Berlanga de Moraes BarrosO metronidazol (MTZ), é uma droga com atividade antibacteriana e antiprotozoárias, utilizada no tratamento de várias infecções. O presente estudo tem por objetivo avaliar a segurança de dois análogos ao.metronidazol, o 1-[2-metanosulfonatoetil]-2-metil-5-nitroimidazol] (MTZ-Ms) e o 1-[2-iodoetil]-2-metil-5-nitroimidazol] (MTZ-I), por meio detestes de toxicidade pré-clínica, agudo e sub agudo. Nos teste de toxicidade aguda foram avaliadas as doses de 300 e 2000 mg/kg. Para o produto MTZ-MS não foi observada morte de nenhum animal. Para o MTZ-I foi detectada a morte de um animal na dose de 2000 mg/kg.Nos testes de toxicidade sub aguda, foram empregadas doses de 200, 400 e 600 mg/kg e para o MTZ-Ms foi utilizada a dose de 1000 mg/kg. Não foi observada alteração no comportamento dos animais tratados com MTZ-MS e com metronidazol, entretanto no grupo tratado com MTZ-I foi observada diminuição do ganho de peso além da morte de doisanimais. Na avaliação bioquímica, alguns parâmetros mostraram diferença significativa embora sem correlação clínica. Na avaliação hematológica foi observado aumento significativo na contagem de linfócitos, leucócitos e hemácias nos grupos tratados commetronidazol e MTZ-MS. Na avaliação histopatológica foi observada hiperplasia das placas de Peyer e hiperplasia da polpa branca do baço em todos os grupos tratados com metronidazol e MTZ-MS e degeneração dos testículos e atresia dos ovários nos grupos tratados com metronidazol na dose de 600 mg/kg e MTZ-MS. Podemos concluir que o aumento dos linfócitos associados à hiperplasia das placas de Peyer e aumento da polpa branca do baço, sugerem um mecanismo de imunoestimulação. MTZ-I demonstrou baixa segurança não sendo interessante prosseguir os estudos, entretanto para o MTZ-MS, maiores investigações são sugeridas uma vez que este fármaco demonstrou ser um produto seguro.UFMGORIGINALmaterial_e_metodos.pdfapplication/pdf91700https://repositorio.ufmg.br//bitstreams/fa730757-9cb5-4862-885f-b0a9f5f394e2/download79d516ccc4efc22dd69230376883e5ceMD51trueAnonymousREADreferencias_bibliograficas.pdfapplication/pdf132603https://repositorio.ufmg.br//bitstreams/e8076b0e-0ce5-4ae4-bee9-79e5c61e618b/download9343df613ab2094f2f371de6746b4a22MD52falseAnonymousREADfolha_de_rosto.pdfapplication/pdf43216https://repositorio.ufmg.br//bitstreams/4d958d76-9125-44c8-addb-35f992368860/download0b0d17377b48e66002b9edfd677f6a70MD53falseAnonymousREADintroducao.pdfapplication/pdf94141https://repositorio.ufmg.br//bitstreams/d7bf0fa3-cffd-4300-a38f-0cbb37ad9eff/downloadee4223754e3afd0177ff9e99bb0c4b6dMD54falseAnonymousREADobjetivos.pdfapplication/pdf44582https://repositorio.ufmg.br//bitstreams/a2639110-9448-4ba1-ac58-f5cc2cdb7dbb/download1322d7d487b5bd75029991f6bedb601aMD55falseAnonymousREADresultados.pdfapplication/pdf3192926https://repositorio.ufmg.br//bitstreams/1266ebdb-146c-4571-ba7a-f85940847906/download70804cf8034225c9acd8e443e63bdf67MD56falseAnonymousREADsumario.pdfapplication/pdf54362https://repositorio.ufmg.br//bitstreams/afc855de-8534-4e27-8561-9ffbb5241344/downloadde851db948962950dcd16933e2d72e66MD57falseAnonymousREADlista_de_figuras_e_siglas_formatado.pdfapplication/pdf68537https://repositorio.ufmg.br//bitstreams/88332a3f-87c6-46e5-a06e-236fa6b61684/download65b2d672f501cda9bd50dbc6fc04f737MD58falseAnonymousREADficha_catalografica.pdfapplication/pdf23041https://repositorio.ufmg.br//bitstreams/7455ba32-d1d0-459c-a5ba-4b72e31f3210/download78aa21352c66501afbec76ffdf6b2237MD59falseAnonymousREADabstract.pdfapplication/pdf54111https://repositorio.ufmg.br//bitstreams/828de27f-33fe-4f99-8fd2-0097bdc17e9a/downloadb8c7f7dc834c379e1a837155c0f3ca08MD510falseAnonymousREADresumo.pdfapplication/pdf43833https://repositorio.ufmg.br//bitstreams/218418a8-4487-498c-be7c-26e00e38c367/download2b9ea7682e2b26c44f486b4c903dc96aMD511falseAnonymousREADdiscussao.pdfapplication/pdf107648https://repositorio.ufmg.br//bitstreams/00d8d727-b2a0-441c-a28d-d8167fae8a75/download14d9785657ef8c91d5bded75a477a227MD512falseAnonymousREADfolha_de_rosto.pdfapplication/pdf43216https://repositorio.ufmg.br//bitstreams/a09d3aec-2e3c-4850-9484-d9a3d9a02c0d/download0b0d17377b48e66002b9edfd677f6a70MD513falseAnonymousREADpaginas_iniciais.pdfapplication/pdf68116https://repositorio.ufmg.br//bitstreams/0b33d323-5bdb-4eb6-b6d5-90ce4d171fc6/download1eba81b4245e844cd0770f256f1574d6MD514falseAnonymousREADlista_de_tabelas_formatada.pdfapplication/pdf40373https://repositorio.ufmg.br//bitstreams/e67df3e8-c5f9-4136-ac3d-861ac7cfba26/downloade79ce93bb3538789b15c45941ac4c6fcMD515falseAnonymousREADTEXTmaterial_e_metodos.pdf.txttext/plain9725https://repositorio.ufmg.br//bitstreams/7ca705c5-9550-4bb3-8cc3-fc09da843801/downloadac2dd95943cfb2c82d0115c2a330a3cbMD516falseAnonymousREADreferencias_bibliograficas.pdf.txttext/plain11786https://repositorio.ufmg.br//bitstreams/df599c12-f570-4882-a7ae-c56d1bfb23da/download82c2236ebc9b9ce55fa329a6e9ad6137MD517falseAnonymousREADfolha_de_rosto.pdf.txttext/plain483https://repositorio.ufmg.br//bitstreams/979bfb78-fd56-4f56-a377-b3d372ddb210/downloadb80443cc0397dbb9a84ec75207b76604MD518falseAnonymousREADintroducao.pdf.txttext/plain8967https://repositorio.ufmg.br//bitstreams/8f802a37-00fd-4e58-b5d3-d827ec1f3308/download3a8b725fd4d20187af30944d731d0915MD519falseAnonymousREADobjetivos.pdf.txttext/plain438https://repositorio.ufmg.br//bitstreams/2a4f38e0-165a-4486-a27e-81fc3b2447c2/downloadebca64531ea6f83ae87ec5622a0c1611MD520falseAnonymousREAD1843/NCFA-7AKL852025-09-08 19:50:45.811open.accessoai:repositorio.ufmg.br:1843/NCFA-7AKL85https://repositorio.ufmg.br/Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2025-09-08T22:50:45Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
| dc.title.none.fl_str_mv |
Avaliação da toxicidade pré-clínica de compostos iodado e mesilado, análogos ao metronidazol |
| title |
Avaliação da toxicidade pré-clínica de compostos iodado e mesilado, análogos ao metronidazol |
| spellingShingle |
Avaliação da toxicidade pré-clínica de compostos iodado e mesilado, análogos ao metronidazol Carla Bonanato de Avelar Toxicidade Testes Medicamentos Efeitos colaterais Agentes antibacterianos Drogas Toxicologia Toxicologia Farmácia toxicidade sub aguda Metronidazol análogos toxicidade aguda Imunoestimulação |
| title_short |
Avaliação da toxicidade pré-clínica de compostos iodado e mesilado, análogos ao metronidazol |
| title_full |
Avaliação da toxicidade pré-clínica de compostos iodado e mesilado, análogos ao metronidazol |
| title_fullStr |
Avaliação da toxicidade pré-clínica de compostos iodado e mesilado, análogos ao metronidazol |
| title_full_unstemmed |
Avaliação da toxicidade pré-clínica de compostos iodado e mesilado, análogos ao metronidazol |
| title_sort |
Avaliação da toxicidade pré-clínica de compostos iodado e mesilado, análogos ao metronidazol |
| author |
Carla Bonanato de Avelar |
| author_facet |
Carla Bonanato de Avelar |
| author_role |
author |
| dc.contributor.author.fl_str_mv |
Carla Bonanato de Avelar |
| dc.subject.por.fl_str_mv |
Toxicidade Testes Medicamentos Efeitos colaterais Agentes antibacterianos Drogas Toxicologia Toxicologia Farmácia |
| topic |
Toxicidade Testes Medicamentos Efeitos colaterais Agentes antibacterianos Drogas Toxicologia Toxicologia Farmácia toxicidade sub aguda Metronidazol análogos toxicidade aguda Imunoestimulação |
| dc.subject.other.none.fl_str_mv |
toxicidade sub aguda Metronidazol análogos toxicidade aguda Imunoestimulação |
| description |
Metronidazole (MTZ) is an antibacterial and antiprotozoal drug used in the treatment of several infections, included those caused by Helicobacter pylori. The present study aimed to evaluate the safety of two MTZ analogues, methanosulfonate (MTZ-Ms) and iodine (MTZI),that showed significant antibacterial activity even to MTZ-resistant strains, in rats through acute and subacute preclinical toxicity. In acute toxicity, 2000 mg/kg of MTZ-Ms was administered and no death was observed. 300 and 2000 mg/kg doses of MTZ-I were administered and one death was observed. In subacute toxicity, no abnormal behavior wasobserved with MTZ and MTZ-Ms. In the group treated with MTZ-I, it was detected a reduction in the weight gain and two death. The biochemical parameters evaluated showed a significant difference without a clinical correlation. Lymphocytes, leukocytes and red blood cells increased in the groups treated with MTZ and MTZ-Ms. Apoptose was observed in thePeyers patches and spleen. In histophatological examination it was observed hyperplasia of Peyers patches and degeneration of the testis and ovary in the groups treated with MTZ and MTZ-Ms. In conclusion, the raise of lymphocytes and Peyers patches suggest imunostimmulation action; MTZ-I presented a low degree of safety, the study suggests thatfurther investigations are needed for MTZ-Ms since it presents a greater degree of safety. |
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2007 |
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2007-03-16 |
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2019-08-11T11:18:35Z 2025-09-08T22:50:45Z |
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2019-08-11T11:18:35Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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por |
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openAccess |
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Universidade Federal de Minas Gerais |
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Universidade Federal de Minas Gerais |
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