Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFS |
Texto Completo: | http://ri.ufs.br/jspui/handle/riufs/16825 |
Resumo: | Sepsis is characterized by an amplified systemic immunoinflammatory response produced by a microorganism. Its pathophysiological mechanism is complex and involves the activation of inflammatory cytokine signaling pathways and oxidative stress. Due to the high mortality in ICU patients, the scientific community has been constantly looking for safe and effective therapies for the treatment of sepsis. And in this context, hydralazine (HDZ) is a strong candidate. Although HDZ is best known as a potent vasodilating substance and has been used frequently in the past five decades as an antihypertensive, due to its safety and low risk of causing toxicity, studies have shown that it also has potent antioxidant properties, especially in inhibition of ROS and RNS formation and sequestration in vivo and in vitro. Thus, the main objective of this study was to evaluate the ability of hydralazine (HDZ) to mitigate mortality, the inflammatory response and oxidative stress induced by sepsis, and to investigate its possible mechanisms of action. Sepsis was induced by the ligation and cecal perforation (CLP) method in male Wistar rats. After surgery, the animals were randomly divided into three groups: sham, sepsis and sepsis + HDZ (1 mg/kg, s.c; 4 h after sepsis induction and after 12-12 hours until 48 h). All groups were monitored for 48 h to assess survival rate, clinical, biochemical and cellular parameters. After euthanasia, blood, spleen, liver and kidneys were collected for analysis of markers of lipid and protein damage, serum blood cytokines, myeloperoxidase activity (MPO) and oxidative stress parameters, through the activity of catalase and superoxide dismutase enzymes. The involvement of the PI3K/Akt pathway was also investigated by western blot in the tissues of the spleen, liver and kidney. Sepsis was successfully induced by the CLP technique. HDZ administration has increased: the survival rate (from 50 to 90%); the temperature (from 33.3 ± 0.2 to 34.5 ± 0.3ºC); blood glucose concentration (from 87.6 ± 2.8 to 106.5 ± 2.1 mg/dL). HDZ treatment reduced: the clinical sepsis severity score (from 10.6 ± 0.51 to 6.5 ± 0.40 u.a.); the lactate concentration (from 36.2 ± 1.5 to 18.03 ± 1.1 mg/dL); the concentrations of cytokines TNF-α, IL-1β and IL-10 (from 10.2 ± 0.3; 99.1 ± 10.7; 1252 ± 325.3, respectively to 4.1 ± 0.4; 19 , 66 ± 4.5; 267 ± 138.1 pg/mL); MPO activity in the spleen, liver and kidney (from 26.02 ± 2.74; 0.11 ± 0.01; 0.20 ± 0.02, respectively to 13.37 ± 0.95; 0.066 ± 0.007; 0.141 ± 0.006 U / g, respectively); TBARS concentrations (from 2.33 ± 0.15; 0.92 ± 0.15; 9.14 ± 0.97 to 1.47 ± 0.07; 0.48 ± 0.06; 4.34 ± 0.36 nmol/mg protein, respectively). In addition, HDZ significantly prevented increased Akt activation in the liver and kidneys, but had no effect on the spleen. HDZ administration largely mitigated the effects of sepsis by improving inflammatory and antioxidant responses through the PI3K/Akt pathway. These findings provide strong evidence that HDZ may be a new therapeutic alternative for the treatment of sepsis. |
id |
UFS-2_d34f4974bfcf2385268094ed106bba67 |
---|---|
oai_identifier_str |
oai:ufs.br:riufs/16825 |
network_acronym_str |
UFS-2 |
network_name_str |
Repositório Institucional da UFS |
repository_id_str |
|
spelling |
Santos, Danillo Menezes dosSantos, Márcio Roberto Viana dosMenezes, Igor Alexandre Cortes2022-11-25T12:51:47Z2022-11-25T12:51:47Z2021SANTOS, Danillo Menezes dos. Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse. 2021. 115 f. Tese (doutorado em Ciências da Saúde) – Universidade Federal de Sergipe, Aracaju, 2021.http://ri.ufs.br/jspui/handle/riufs/16825Sepsis is characterized by an amplified systemic immunoinflammatory response produced by a microorganism. Its pathophysiological mechanism is complex and involves the activation of inflammatory cytokine signaling pathways and oxidative stress. Due to the high mortality in ICU patients, the scientific community has been constantly looking for safe and effective therapies for the treatment of sepsis. And in this context, hydralazine (HDZ) is a strong candidate. Although HDZ is best known as a potent vasodilating substance and has been used frequently in the past five decades as an antihypertensive, due to its safety and low risk of causing toxicity, studies have shown that it also has potent antioxidant properties, especially in inhibition of ROS and RNS formation and sequestration in vivo and in vitro. Thus, the main objective of this study was to evaluate the ability of hydralazine (HDZ) to mitigate mortality, the inflammatory response and oxidative stress induced by sepsis, and to investigate its possible mechanisms of action. Sepsis was induced by the ligation and cecal perforation (CLP) method in male Wistar rats. After surgery, the animals were randomly divided into three groups: sham, sepsis and sepsis + HDZ (1 mg/kg, s.c; 4 h after sepsis induction and after 12-12 hours until 48 h). All groups were monitored for 48 h to assess survival rate, clinical, biochemical and cellular parameters. After euthanasia, blood, spleen, liver and kidneys were collected for analysis of markers of lipid and protein damage, serum blood cytokines, myeloperoxidase activity (MPO) and oxidative stress parameters, through the activity of catalase and superoxide dismutase enzymes. The involvement of the PI3K/Akt pathway was also investigated by western blot in the tissues of the spleen, liver and kidney. Sepsis was successfully induced by the CLP technique. HDZ administration has increased: the survival rate (from 50 to 90%); the temperature (from 33.3 ± 0.2 to 34.5 ± 0.3ºC); blood glucose concentration (from 87.6 ± 2.8 to 106.5 ± 2.1 mg/dL). HDZ treatment reduced: the clinical sepsis severity score (from 10.6 ± 0.51 to 6.5 ± 0.40 u.a.); the lactate concentration (from 36.2 ± 1.5 to 18.03 ± 1.1 mg/dL); the concentrations of cytokines TNF-α, IL-1β and IL-10 (from 10.2 ± 0.3; 99.1 ± 10.7; 1252 ± 325.3, respectively to 4.1 ± 0.4; 19 , 66 ± 4.5; 267 ± 138.1 pg/mL); MPO activity in the spleen, liver and kidney (from 26.02 ± 2.74; 0.11 ± 0.01; 0.20 ± 0.02, respectively to 13.37 ± 0.95; 0.066 ± 0.007; 0.141 ± 0.006 U / g, respectively); TBARS concentrations (from 2.33 ± 0.15; 0.92 ± 0.15; 9.14 ± 0.97 to 1.47 ± 0.07; 0.48 ± 0.06; 4.34 ± 0.36 nmol/mg protein, respectively). In addition, HDZ significantly prevented increased Akt activation in the liver and kidneys, but had no effect on the spleen. HDZ administration largely mitigated the effects of sepsis by improving inflammatory and antioxidant responses through the PI3K/Akt pathway. These findings provide strong evidence that HDZ may be a new therapeutic alternative for the treatment of sepsis.A sepse é caracterizada por uma resposta imunoinflamatória sistêmica amplificada produzida por um microrganismo. Seu mecanismo fisiopatológico é complexo e envolve a ativação de vias de sinalização de citocinas inflamatórias e estresse oxidativo. Devido à alta mortalidade em pacientes internados em UTI, a comunidade científica tem buscado constantemente terapias seguras e eficazes para o tratamento da sepse. E, nesse contexto, a hidralazina (HDZ) é um forte candidato. Embora a HDZ seja mais conhecida como uma potente substância vasodilatadora e tenha sido frequentemente usado nas últimas cinco décadas como anti-hipertensivo, devido a sua segurança e ao baixo risco de causar toxicidade, estudos têm mostrado que ela também possui potentes propriedades antioxidantes, principalmente em relação à inibição da formação e sequestro de ERO e ERN in vivo e in vitro. Assim, o principal objetivo deste estudo foi avaliar a capacidade da hidralazina (HDZ) em mitigar a mortalidade, a resposta inflamatória e o estresse oxidativo induzida pela sepse, e investigar seus possíveis mecanismos de ações. A sepse foi induzida pelo método de ligadura e perfuração cecal (CLP) em ratos Wistar machos. Após a cirurgia, os animais foram divididos aleatoriamente em três grupos: sham, sepse e sepse + HDZ (1 mg/kg, s.c; 4 h após a indução da sepse e depois de 12-12 horas até tempo de 48 h). Todos os grupos foram monitorados por 48 h para avaliar a taxa de sobrevivência, parâmetros clínicos, bioquímicos e celulares. Após a eutanásia, o sangue, baço, fígado e rins foram coletados para análise dos marcadores de danos lipídicos e proteicos, citocinas séricas do sangue, atividade de mieloperoxidase (MPO) e parâmetros de estresse oxidativo, através da atividade das enzimas catalase e superóxido dismutase. O envolvimento da via PI3K/Akt também foi investigado por western Blot nos tecidos do baço, fígado e rim. A sepse foi induzida com sucesso pela técnica CLP. A administração com HDZ aumentou: a taxa de sobrevivência (de 50 para 90%); a temperatura (de 33,3 ± 0,2 para 34,5 ± 0,3ºC); a concentração da glicemia (de 87,6 ± 2,8 para 106.5 ± 2.1 mg/dL). O tratamento com HDZ reduziu: o escore de gravidade clínica de sepse (de 10,6 ± 0,51 para 6,5 ± 0,40 u.a.); a concentração do lactato (de 36,2 ± 1,5 para 18,03 ± 1,1 mg/dL); as concentrações das citocinas TNF-α, IL-1β e IL-10 (de 10,2 ± 0,3; 99,1 ± 10,7; 1252 ± 325,3, respectivamente para 4,1 ± 0,4; 19,66 ± 4,5; 267 ± 138,1 pg/mL); a atividade da MPO no baço, fígado e rim (de 26,02 ± 2,74; 0,11 ± 0,01; 0,20 ± 0,02, respectivamente para 13,37 ± 0,95; 0,066 ± 0,007; 0,141 ± 0,006 U/g, respectivamente); as concentrações de TBARS (de 2,33 ± 0,15; 0,92 ± 0,15; 9,14 ± 0,97 para 1,47 ± 0,07; 0,48 ± 0,06; 4,34 ± 0,36 nmol/mg de proteína, respectivamente). Além disso, a HDZ preveniu significativamente o aumento da ativação da Akt no fígado e rins, mas não teve efeito no baço. A administração com HDZ mitigou amplamente os efeitos da sepse ao melhorar as respostas inflamatórias e antioxidantes por meio da via PI3K/Akt. Esses achados fornecem fortes evidências de que o HDZ pode ser uma nova alternativa terapêutica para o tratamento da sepse.AracajuporCiências da saúdeSepseHidralazinaSobrevidaImunidade celularCitocinasAntioxidanteHealth SciencesSepsisHydralazineSurvivalCellular immunityCytokinesAntioxidantCIENCIAS DA SAUDEEfeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisPós-Graduação em Ciências da SaúdeUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/16825/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALDANILLO_MENEZES_DOS_SANTOS.pdfDANILLO_MENEZES_DOS_SANTOS.pdfapplication/pdf2140756https://ri.ufs.br/jspui/bitstream/riufs/16825/2/DANILLO_MENEZES_DOS_SANTOS.pdfed818bff3d90c630820887eaddc3ff1bMD52TEXTDANILLO_MENEZES_DOS_SANTOS.pdf.txtDANILLO_MENEZES_DOS_SANTOS.pdf.txtExtracted texttext/plain200263https://ri.ufs.br/jspui/bitstream/riufs/16825/3/DANILLO_MENEZES_DOS_SANTOS.pdf.txt7e21153bf65b9567d39ca5b6056c45afMD53THUMBNAILDANILLO_MENEZES_DOS_SANTOS.pdf.jpgDANILLO_MENEZES_DOS_SANTOS.pdf.jpgGenerated Thumbnailimage/jpeg1233https://ri.ufs.br/jspui/bitstream/riufs/16825/4/DANILLO_MENEZES_DOS_SANTOS.pdf.jpg3e5fcf9ee2dbe1749813b2a3dbd73d61MD54riufs/168252022-11-28 12:02:51.41oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2022-11-28T15:02:51Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.pt_BR.fl_str_mv |
Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse |
title |
Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse |
spellingShingle |
Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse Santos, Danillo Menezes dos Ciências da saúde Sepse Hidralazina Sobrevida Imunidade celular Citocinas Antioxidante Health Sciences Sepsis Hydralazine Survival Cellular immunity Cytokines Antioxidant CIENCIAS DA SAUDE |
title_short |
Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse |
title_full |
Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse |
title_fullStr |
Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse |
title_full_unstemmed |
Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse |
title_sort |
Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse |
author |
Santos, Danillo Menezes dos |
author_facet |
Santos, Danillo Menezes dos |
author_role |
author |
dc.contributor.author.fl_str_mv |
Santos, Danillo Menezes dos |
dc.contributor.advisor1.fl_str_mv |
Santos, Márcio Roberto Viana dos |
dc.contributor.advisor-co1.fl_str_mv |
Menezes, Igor Alexandre Cortes |
contributor_str_mv |
Santos, Márcio Roberto Viana dos Menezes, Igor Alexandre Cortes |
dc.subject.por.fl_str_mv |
Ciências da saúde Sepse Hidralazina Sobrevida Imunidade celular Citocinas Antioxidante |
topic |
Ciências da saúde Sepse Hidralazina Sobrevida Imunidade celular Citocinas Antioxidante Health Sciences Sepsis Hydralazine Survival Cellular immunity Cytokines Antioxidant CIENCIAS DA SAUDE |
dc.subject.eng.fl_str_mv |
Health Sciences Sepsis Hydralazine Survival Cellular immunity Cytokines Antioxidant |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE |
description |
Sepsis is characterized by an amplified systemic immunoinflammatory response produced by a microorganism. Its pathophysiological mechanism is complex and involves the activation of inflammatory cytokine signaling pathways and oxidative stress. Due to the high mortality in ICU patients, the scientific community has been constantly looking for safe and effective therapies for the treatment of sepsis. And in this context, hydralazine (HDZ) is a strong candidate. Although HDZ is best known as a potent vasodilating substance and has been used frequently in the past five decades as an antihypertensive, due to its safety and low risk of causing toxicity, studies have shown that it also has potent antioxidant properties, especially in inhibition of ROS and RNS formation and sequestration in vivo and in vitro. Thus, the main objective of this study was to evaluate the ability of hydralazine (HDZ) to mitigate mortality, the inflammatory response and oxidative stress induced by sepsis, and to investigate its possible mechanisms of action. Sepsis was induced by the ligation and cecal perforation (CLP) method in male Wistar rats. After surgery, the animals were randomly divided into three groups: sham, sepsis and sepsis + HDZ (1 mg/kg, s.c; 4 h after sepsis induction and after 12-12 hours until 48 h). All groups were monitored for 48 h to assess survival rate, clinical, biochemical and cellular parameters. After euthanasia, blood, spleen, liver and kidneys were collected for analysis of markers of lipid and protein damage, serum blood cytokines, myeloperoxidase activity (MPO) and oxidative stress parameters, through the activity of catalase and superoxide dismutase enzymes. The involvement of the PI3K/Akt pathway was also investigated by western blot in the tissues of the spleen, liver and kidney. Sepsis was successfully induced by the CLP technique. HDZ administration has increased: the survival rate (from 50 to 90%); the temperature (from 33.3 ± 0.2 to 34.5 ± 0.3ºC); blood glucose concentration (from 87.6 ± 2.8 to 106.5 ± 2.1 mg/dL). HDZ treatment reduced: the clinical sepsis severity score (from 10.6 ± 0.51 to 6.5 ± 0.40 u.a.); the lactate concentration (from 36.2 ± 1.5 to 18.03 ± 1.1 mg/dL); the concentrations of cytokines TNF-α, IL-1β and IL-10 (from 10.2 ± 0.3; 99.1 ± 10.7; 1252 ± 325.3, respectively to 4.1 ± 0.4; 19 , 66 ± 4.5; 267 ± 138.1 pg/mL); MPO activity in the spleen, liver and kidney (from 26.02 ± 2.74; 0.11 ± 0.01; 0.20 ± 0.02, respectively to 13.37 ± 0.95; 0.066 ± 0.007; 0.141 ± 0.006 U / g, respectively); TBARS concentrations (from 2.33 ± 0.15; 0.92 ± 0.15; 9.14 ± 0.97 to 1.47 ± 0.07; 0.48 ± 0.06; 4.34 ± 0.36 nmol/mg protein, respectively). In addition, HDZ significantly prevented increased Akt activation in the liver and kidneys, but had no effect on the spleen. HDZ administration largely mitigated the effects of sepsis by improving inflammatory and antioxidant responses through the PI3K/Akt pathway. These findings provide strong evidence that HDZ may be a new therapeutic alternative for the treatment of sepsis. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021 |
dc.date.accessioned.fl_str_mv |
2022-11-25T12:51:47Z |
dc.date.available.fl_str_mv |
2022-11-25T12:51:47Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
SANTOS, Danillo Menezes dos. Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse. 2021. 115 f. Tese (doutorado em Ciências da Saúde) – Universidade Federal de Sergipe, Aracaju, 2021. |
dc.identifier.uri.fl_str_mv |
http://ri.ufs.br/jspui/handle/riufs/16825 |
identifier_str_mv |
SANTOS, Danillo Menezes dos. Efeito da hidralazina na sobrevida, na resposta inflamatória e no estresse oxidativo em modelo animal de sepse. 2021. 115 f. Tese (doutorado em Ciências da Saúde) – Universidade Federal de Sergipe, Aracaju, 2021. |
url |
http://ri.ufs.br/jspui/handle/riufs/16825 |
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.publisher.program.fl_str_mv |
Pós-Graduação em Ciências da Saúde |
dc.publisher.initials.fl_str_mv |
Universidade Federal de Sergipe |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFS instname:Universidade Federal de Sergipe (UFS) instacron:UFS |
instname_str |
Universidade Federal de Sergipe (UFS) |
instacron_str |
UFS |
institution |
UFS |
reponame_str |
Repositório Institucional da UFS |
collection |
Repositório Institucional da UFS |
bitstream.url.fl_str_mv |
https://ri.ufs.br/jspui/bitstream/riufs/16825/1/license.txt https://ri.ufs.br/jspui/bitstream/riufs/16825/2/DANILLO_MENEZES_DOS_SANTOS.pdf https://ri.ufs.br/jspui/bitstream/riufs/16825/3/DANILLO_MENEZES_DOS_SANTOS.pdf.txt https://ri.ufs.br/jspui/bitstream/riufs/16825/4/DANILLO_MENEZES_DOS_SANTOS.pdf.jpg |
bitstream.checksum.fl_str_mv |
098cbbf65c2c15e1fb2e49c5d306a44c ed818bff3d90c630820887eaddc3ff1b 7e21153bf65b9567d39ca5b6056c45af 3e5fcf9ee2dbe1749813b2a3dbd73d61 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS) |
repository.mail.fl_str_mv |
repositorio@academico.ufs.br |
_version_ |
1802110734482538496 |