Disseleneto de difenila e selenito de sódio associado à trimetoprima e sulfametoxazol em toxoplasmose experimental: influência na atividade de biomarcadores de estresse oxidativo e modulação de citocinas
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/28171 |
Resumo: | Toxoplasmosis is a zoonosis of worldwide geographic distribution, caused by Toxoplasma gondii, an obligate intracellular protozoan with, in certain regions, high-impact medical-veterinary; being considered one of the most widespread infectious diseases. The aim of this study was to assess the effect of sulfamethoxazole and trimethoprim (ST) associated with diphenyl diselenide (DPDS) and sodium selenite (SSe) in experimental toxoplasmosis, on oxidant/antioxidant biomarkers and cytokine levels. Therefore, this study evaluated the levels of thiobarbituric acid reactive substances (TBARS), advanced oxidation protein products (AOPP) and glutathione reductase (GR), as well as on the modulation of inflammatory response through assessment of INF-γ and IL-10. For that eighty four adult male BALB/c mice were used, divided in two seven groups. Group A was used as negative control. The mice from groups B to G were infected intraperitoneally with 1.2x107 tachyzoites (RH strain). Of these, the group B represented the positive control; groups C to G represented the treatment groups, as follow: C: T. gondii plus ST; D: T. gondii supplemented by SSe; E: T. gondii plus DPDS; F T. gondii treated with ST associated with SSe; and G: T. gondii plus ST associated with DPDS. Samples of blood and liver were collected and analyzed on days 4 and 20 post-infection (p.i.). As results, it was possible to observe that TBARS levels significantly increased (P<0.05) in groups B, C and F on day 4 p.i., while it was reduced (P<0.05) in groups C, F and G on day 20 p.i. when these data were compared with group A. Levels of AOPP significantly increased (P<0.001) in groups C and G on day 4 p.i., and it was reduced in groups C, F and G (P<0.001) on day 20 p.i. when compared with group A. Additionally, the activity of GR significantly (P<0.01) increased on day 4 p.i. in group G when it was compared with the control group. Cytokine levels showed INF- significantly increased (P<0.001) in both periods, day 4 (groups B, C, F and G) and 20 p.i. (groups C, F and G) when compared with group A. Levels of IL-10 were significantly reduced (P<0.001) on day 4 p.i. in group B, while at the same period it was increased (P<0.001) in groups C and G when compared with group A. On day 20 p.i. IL-10 had its levels increased (P<0.001) in groups F and G, when compared with control group. Therefore, our results highlighted that inorganic (sodium selenite) and organic (diphenyl diselenide) forms of selenium associated with the chemotherapy (a common therapeutic choice in toxoplasmosis) were able to reduce the lipid peroxidation and protein oxidation, manly during the acute phase of the experimental infection, as well as it provided a immunologic balance between the production of pro and anti-inflammatory cytokines, avoiding over production of pro-inflammatory cytokines. |
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Disseleneto de difenila e selenito de sódio associado à trimetoprima e sulfametoxazol em toxoplasmose experimental: influência na atividade de biomarcadores de estresse oxidativo e modulação de citocinasDiphenyl diselenide and sodium selenite associated with trimetoprima and sulfametoxazol in experimental toxoplasmosis: influence on oxidant/antioxidant biomarkers and cytokine modulationToxoplasmoseCompostos de selênioPeroxidação lipídicaOxidação de proteínasCitocinasToxoplasmosisSelenium compoundsLipid peroxidationProtein oxidationCytokinesCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAToxoplasmosis is a zoonosis of worldwide geographic distribution, caused by Toxoplasma gondii, an obligate intracellular protozoan with, in certain regions, high-impact medical-veterinary; being considered one of the most widespread infectious diseases. The aim of this study was to assess the effect of sulfamethoxazole and trimethoprim (ST) associated with diphenyl diselenide (DPDS) and sodium selenite (SSe) in experimental toxoplasmosis, on oxidant/antioxidant biomarkers and cytokine levels. Therefore, this study evaluated the levels of thiobarbituric acid reactive substances (TBARS), advanced oxidation protein products (AOPP) and glutathione reductase (GR), as well as on the modulation of inflammatory response through assessment of INF-γ and IL-10. For that eighty four adult male BALB/c mice were used, divided in two seven groups. Group A was used as negative control. The mice from groups B to G were infected intraperitoneally with 1.2x107 tachyzoites (RH strain). Of these, the group B represented the positive control; groups C to G represented the treatment groups, as follow: C: T. gondii plus ST; D: T. gondii supplemented by SSe; E: T. gondii plus DPDS; F T. gondii treated with ST associated with SSe; and G: T. gondii plus ST associated with DPDS. Samples of blood and liver were collected and analyzed on days 4 and 20 post-infection (p.i.). As results, it was possible to observe that TBARS levels significantly increased (P<0.05) in groups B, C and F on day 4 p.i., while it was reduced (P<0.05) in groups C, F and G on day 20 p.i. when these data were compared with group A. Levels of AOPP significantly increased (P<0.001) in groups C and G on day 4 p.i., and it was reduced in groups C, F and G (P<0.001) on day 20 p.i. when compared with group A. Additionally, the activity of GR significantly (P<0.01) increased on day 4 p.i. in group G when it was compared with the control group. Cytokine levels showed INF- significantly increased (P<0.001) in both periods, day 4 (groups B, C, F and G) and 20 p.i. (groups C, F and G) when compared with group A. Levels of IL-10 were significantly reduced (P<0.001) on day 4 p.i. in group B, while at the same period it was increased (P<0.001) in groups C and G when compared with group A. On day 20 p.i. IL-10 had its levels increased (P<0.001) in groups F and G, when compared with control group. Therefore, our results highlighted that inorganic (sodium selenite) and organic (diphenyl diselenide) forms of selenium associated with the chemotherapy (a common therapeutic choice in toxoplasmosis) were able to reduce the lipid peroxidation and protein oxidation, manly during the acute phase of the experimental infection, as well as it provided a immunologic balance between the production of pro and anti-inflammatory cytokines, avoiding over production of pro-inflammatory cytokines.A toxoplasmose é uma zoonose de distribuição geográfica mundial, causada por Toxoplasma gondii, um protozoário intracelular obrigatório, podendo apresentar, em determinadas regiões, grande impacto médico- veterinário; sendo considerada uma das enfermidades infecciosas mais difundidas dentre as transmissíveis. O objetivo deste estudo foi avaliar o efeito da associação entre trimetoprima e sulfametoxazol (ST) com disseleneto de difenila (DPDS) e selenito de sódio (SSe) em um modelo experimental de toxoplasmose, sobre biomarcadores de estresse oxidativo e nos níveis de citocinas. Portanto, este estudo avaliou os níveis de substâncias reativas ao ácido tiobarbitúrico (TBARS), produtos avançados de oxidação de proteínas (AOPP) e a atividade da glutationa redutase (GR), assim como a modulação da resposta inflamatória por meio da avaliação dos níveis de INF-γ e IL-10. Para estes fins, oitenta e quatro camundongos BALB/c adultos, machos, foram utilizados. Estes foram divididos em sete grupos, onde o grupo A serviu como controle negativo. Os animais dos grupos B ao G foram infectados intraperitonealmente com 1.2x107 taquizoítos (cepa RH). Destes, o grupo B representou o controle positivo; enquanto que os grupos C a G representaram os grupos de tratamento, como definido a seguir: grupo C: infectados com T. gondii e tratados com ST; grupo D: infectados com T. gondii e suplementados com SSe; grupo E: infectados com T. gondii e suplementados com DPDS; grupo F: infectados com T. gondii e tratados com ST associada a SSe; e grupo G: infectados com T. gondii e tratados com ST associado ao DPDS. As amostras de sangue e de fígado foram coletadas e analisadas nos dias 4 e 20 pós-infecção (pi). Como resultado foi possível observar que os níveis de TBARS aumentaram significativamente (P<0,05) nos grupos B, C e F no dia 4 pi, ao mesmo tempo que os níveis deste mesmo biomarcador foram reduzidos (P<0,05) nos grupos C, F e G no dia 20 pi, quando esses dados foram comparados com o grupo A. Os níveis de AOPP aumentaram significativamente (P<0,001) nos grupos C e G no dia 4 do pi, ao passo que os níveis desse biomarcador foram reduzidos nos grupos C, F e G (P<0,001) no dia 20 pi, quando comparado com o grupo A. Adicionalmente, a atividade de GR aumentou significativamente (P<0,01) no dia 4 pi no grupo G, quando este foi comparado com o grupo controle. Os níveis de INF-y aumentaram significativamente (P<0,001) em ambos os períodos, no dia 4 (grupos B, C, F e G) e 20 pi (grupos C, F e G), quando comparado ao grupo A. Os níveis de IL-10 estavam significativamente reduzidos (P<0,001) no dia 4 pi no grupo B, enquanto que no mesmo período este estava aumentado (P<0,001) nos grupos C e G, quando comparado com o grupo A. No dia 20 pi os níveis de IL-10 estavam aumentados (P<0,001) nos grupos F e G, quando comparado com o grupo controle. Desta maneira, nossos resultados evidenciaram que as formas inorgânica (Selenito de sódio) e orgânica (disseleneto de difenila) de selênio quando associadas com a quimioterapia foram capazes de reduzir a peroxidação lipídica e oxidação de proteína, principalmente durante a fase aguda da infecção experimental, assim como proporcionou um balanço imunológico entre a produção de citocinas pro e anti-inflamatórios, evitando assim a produção excessiva de citocinas pró-inflamatórias.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaCentro de Ciências da Saúdede la Rue, Mario Luizhttp://lattes.cnpq.br/5733736449142334Leal, Daniela Bitencourt RosaThomé, Gustavo RobertoBarbosa, Cleber Francisco2023-03-13T15:20:32Z2023-03-13T15:20:32Z2014-12-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/28171porAttribution-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:UFSM2023-03-13T15:20:32Zoai:repositorio.ufsm.br:1/28171Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2023-03-13T15:20:32Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Disseleneto de difenila e selenito de sódio associado à trimetoprima e sulfametoxazol em toxoplasmose experimental: influência na atividade de biomarcadores de estresse oxidativo e modulação de citocinas Diphenyl diselenide and sodium selenite associated with trimetoprima and sulfametoxazol in experimental toxoplasmosis: influence on oxidant/antioxidant biomarkers and cytokine modulation |
title |
Disseleneto de difenila e selenito de sódio associado à trimetoprima e sulfametoxazol em toxoplasmose experimental: influência na atividade de biomarcadores de estresse oxidativo e modulação de citocinas |
spellingShingle |
Disseleneto de difenila e selenito de sódio associado à trimetoprima e sulfametoxazol em toxoplasmose experimental: influência na atividade de biomarcadores de estresse oxidativo e modulação de citocinas Barbosa, Cleber Francisco Toxoplasmose Compostos de selênio Peroxidação lipídica Oxidação de proteínas Citocinas Toxoplasmosis Selenium compounds Lipid peroxidation Protein oxidation Cytokines CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Disseleneto de difenila e selenito de sódio associado à trimetoprima e sulfametoxazol em toxoplasmose experimental: influência na atividade de biomarcadores de estresse oxidativo e modulação de citocinas |
title_full |
Disseleneto de difenila e selenito de sódio associado à trimetoprima e sulfametoxazol em toxoplasmose experimental: influência na atividade de biomarcadores de estresse oxidativo e modulação de citocinas |
title_fullStr |
Disseleneto de difenila e selenito de sódio associado à trimetoprima e sulfametoxazol em toxoplasmose experimental: influência na atividade de biomarcadores de estresse oxidativo e modulação de citocinas |
title_full_unstemmed |
Disseleneto de difenila e selenito de sódio associado à trimetoprima e sulfametoxazol em toxoplasmose experimental: influência na atividade de biomarcadores de estresse oxidativo e modulação de citocinas |
title_sort |
Disseleneto de difenila e selenito de sódio associado à trimetoprima e sulfametoxazol em toxoplasmose experimental: influência na atividade de biomarcadores de estresse oxidativo e modulação de citocinas |
author |
Barbosa, Cleber Francisco |
author_facet |
Barbosa, Cleber Francisco |
author_role |
author |
dc.contributor.none.fl_str_mv |
de la Rue, Mario Luiz http://lattes.cnpq.br/5733736449142334 Leal, Daniela Bitencourt Rosa Thomé, Gustavo Roberto |
dc.contributor.author.fl_str_mv |
Barbosa, Cleber Francisco |
dc.subject.por.fl_str_mv |
Toxoplasmose Compostos de selênio Peroxidação lipídica Oxidação de proteínas Citocinas Toxoplasmosis Selenium compounds Lipid peroxidation Protein oxidation Cytokines CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Toxoplasmose Compostos de selênio Peroxidação lipídica Oxidação de proteínas Citocinas Toxoplasmosis Selenium compounds Lipid peroxidation Protein oxidation Cytokines CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Toxoplasmosis is a zoonosis of worldwide geographic distribution, caused by Toxoplasma gondii, an obligate intracellular protozoan with, in certain regions, high-impact medical-veterinary; being considered one of the most widespread infectious diseases. The aim of this study was to assess the effect of sulfamethoxazole and trimethoprim (ST) associated with diphenyl diselenide (DPDS) and sodium selenite (SSe) in experimental toxoplasmosis, on oxidant/antioxidant biomarkers and cytokine levels. Therefore, this study evaluated the levels of thiobarbituric acid reactive substances (TBARS), advanced oxidation protein products (AOPP) and glutathione reductase (GR), as well as on the modulation of inflammatory response through assessment of INF-γ and IL-10. For that eighty four adult male BALB/c mice were used, divided in two seven groups. Group A was used as negative control. The mice from groups B to G were infected intraperitoneally with 1.2x107 tachyzoites (RH strain). Of these, the group B represented the positive control; groups C to G represented the treatment groups, as follow: C: T. gondii plus ST; D: T. gondii supplemented by SSe; E: T. gondii plus DPDS; F T. gondii treated with ST associated with SSe; and G: T. gondii plus ST associated with DPDS. Samples of blood and liver were collected and analyzed on days 4 and 20 post-infection (p.i.). As results, it was possible to observe that TBARS levels significantly increased (P<0.05) in groups B, C and F on day 4 p.i., while it was reduced (P<0.05) in groups C, F and G on day 20 p.i. when these data were compared with group A. Levels of AOPP significantly increased (P<0.001) in groups C and G on day 4 p.i., and it was reduced in groups C, F and G (P<0.001) on day 20 p.i. when compared with group A. Additionally, the activity of GR significantly (P<0.01) increased on day 4 p.i. in group G when it was compared with the control group. Cytokine levels showed INF- significantly increased (P<0.001) in both periods, day 4 (groups B, C, F and G) and 20 p.i. (groups C, F and G) when compared with group A. Levels of IL-10 were significantly reduced (P<0.001) on day 4 p.i. in group B, while at the same period it was increased (P<0.001) in groups C and G when compared with group A. On day 20 p.i. IL-10 had its levels increased (P<0.001) in groups F and G, when compared with control group. Therefore, our results highlighted that inorganic (sodium selenite) and organic (diphenyl diselenide) forms of selenium associated with the chemotherapy (a common therapeutic choice in toxoplasmosis) were able to reduce the lipid peroxidation and protein oxidation, manly during the acute phase of the experimental infection, as well as it provided a immunologic balance between the production of pro and anti-inflammatory cytokines, avoiding over production of pro-inflammatory cytokines. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-12-18 2023-03-13T15:20:32Z 2023-03-13T15:20:32Z |
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/1/28171 |
url |
http://repositorio.ufsm.br/handle/1/28171 |
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 Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
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 |
_version_ |
1805922174172659712 |