Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo

Autores
Gomez, Fernando Daniel; Sacerdoti, Flavia; Toytoyndjian, Eugenia Victoria; Ibarra, Cristina Adriana; Amaral, María Marta
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Typical HemolyticUremic Syndrome (HUS) is a complication of Shiga toxin (Stx)-producingEscherichia coli (STEC) infection and the most frequent cause of acute renalfailure in children in Argentina. Stx2 binds to globotriaosylceramide (Gb3)receptor and causes direct damage on human renal microvascular endothelialcells (HGEC). Previously, we found that Eliglustat (EG), a Gb3 synthesisinhibitor, prevents the cytotoxic effects of Stx2 on HGEC. In this work, we evaluatedthe action of EG against the effects of Stx2 in vivo. Male BALB/c mice atweaning (17-21 days) received 3 doses of EG (0.6 mg/g body weight (bwt)administered intraperitoneally (i.p.) every 24 h. After a rest period of 5days, mice were i.p. injected with a lethal (1ng/g bwt) or sublethal (0.1 ng/gbwt) dose of Stx2 (EG+Stx2) or PBS (EG). Two additional groups of mice withoutEG pre-treatment were injected one with PBS (Ctrl) and another with Stx2(Stx2). Survival, body weight (Δ weight= body weight after Stx2 or PBS injection-bodyweight at a day before injection) and food intake were registered daily. EG didnot affect body weight gain (Δ weight: EG: 0.61 ± 0.07 g vs. Ctrl: 0.76 ± 0.09g; n=3, ns). After Stx2 lethal dose treatment, EG+Stx2 mice showed a bodyweight decrease and a survival time (48-72 h) similar to Stx2 mice. On thecontrary, after 3 days of Stx2 sublethal dose injection, while Stx2 miceexhibited piloerection and inactivity and body weight loss, EG+Stx2 mice did notshow signs of illness and gained weight (Δ weight: EG+Stx2: 0.81 ± 0.09 vs.Stx2: -0.65 ± 0.05 g; n=3, p<0.05). Body weight loss in Stx2 mice wasassociated with a significant decrease (70%) in food intake, unlike EGpre-treated mice that reduced intake by only 15% (n=3, p<0.05). Theseresults suggest that EG may reduce the disease symptoms caused by Stx2, such aspoor appetite and the resulting body weight loss. Future studies will analyzeif EG prevents the renal damage and will improve EG treatment to avoidmortality.
Fil: Gomez, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Toytoyndjian, Eugenia Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y LIII Reunión Anual de la Asociación Argentina de Fisiología
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Fisiología
Materia
eliglustat
shiga toxin
mice
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/193264
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivoGomez, Fernando DanielSacerdoti, FlaviaToytoyndjian, Eugenia VictoriaIbarra, Cristina AdrianaAmaral, María Martaeliglustatshiga toxinmicehttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Typical HemolyticUremic Syndrome (HUS) is a complication of Shiga toxin (Stx)-producingEscherichia coli (STEC) infection and the most frequent cause of acute renalfailure in children in Argentina. Stx2 binds to globotriaosylceramide (Gb3)receptor and causes direct damage on human renal microvascular endothelialcells (HGEC). Previously, we found that Eliglustat (EG), a Gb3 synthesisinhibitor, prevents the cytotoxic effects of Stx2 on HGEC. In this work, we evaluatedthe action of EG against the effects of Stx2 in vivo. Male BALB/c mice atweaning (17-21 days) received 3 doses of EG (0.6 mg/g body weight (bwt)administered intraperitoneally (i.p.) every 24 h. After a rest period of 5days, mice were i.p. injected with a lethal (1ng/g bwt) or sublethal (0.1 ng/gbwt) dose of Stx2 (EG+Stx2) or PBS (EG). Two additional groups of mice withoutEG pre-treatment were injected one with PBS (Ctrl) and another with Stx2(Stx2). Survival, body weight (Δ weight= body weight after Stx2 or PBS injection-bodyweight at a day before injection) and food intake were registered daily. EG didnot affect body weight gain (Δ weight: EG: 0.61 ± 0.07 g vs. Ctrl: 0.76 ± 0.09g; n=3, ns). After Stx2 lethal dose treatment, EG+Stx2 mice showed a bodyweight decrease and a survival time (48-72 h) similar to Stx2 mice. On thecontrary, after 3 days of Stx2 sublethal dose injection, while Stx2 miceexhibited piloerection and inactivity and body weight loss, EG+Stx2 mice did notshow signs of illness and gained weight (Δ weight: EG+Stx2: 0.81 ± 0.09 vs.Stx2: -0.65 ± 0.05 g; n=3, p<0.05). Body weight loss in Stx2 mice wasassociated with a significant decrease (70%) in food intake, unlike EGpre-treated mice that reduced intake by only 15% (n=3, p<0.05). Theseresults suggest that EG may reduce the disease symptoms caused by Stx2, such aspoor appetite and the resulting body weight loss. Future studies will analyzeif EG prevents the renal damage and will improve EG treatment to avoidmortality.Fil: Gomez, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Toytoyndjian, Eugenia Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaLXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y LIII Reunión Anual de la Asociación Argentina de FisiologíaArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de FisiologíaFundación Revista Medicina2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/193264Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y LIII Reunión Anual de la Asociación Argentina de Fisiología; Argentina; 2020; 84-840025-7680CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/reunion-anualNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:03Zoai:ri.conicet.gov.ar:11336/193264instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:52:03.415CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo
title Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo
spellingShingle Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo
Gomez, Fernando Daniel
eliglustat
shiga toxin
mice
title_short Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo
title_full Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo
title_fullStr Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo
title_full_unstemmed Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo
title_sort Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo
dc.creator.none.fl_str_mv Gomez, Fernando Daniel
Sacerdoti, Flavia
Toytoyndjian, Eugenia Victoria
Ibarra, Cristina Adriana
Amaral, María Marta
author Gomez, Fernando Daniel
author_facet Gomez, Fernando Daniel
Sacerdoti, Flavia
Toytoyndjian, Eugenia Victoria
Ibarra, Cristina Adriana
Amaral, María Marta
author_role author
author2 Sacerdoti, Flavia
Toytoyndjian, Eugenia Victoria
Ibarra, Cristina Adriana
Amaral, María Marta
author2_role author
author
author
author
dc.subject.none.fl_str_mv eliglustat
shiga toxin
mice
topic eliglustat
shiga toxin
mice
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Typical HemolyticUremic Syndrome (HUS) is a complication of Shiga toxin (Stx)-producingEscherichia coli (STEC) infection and the most frequent cause of acute renalfailure in children in Argentina. Stx2 binds to globotriaosylceramide (Gb3)receptor and causes direct damage on human renal microvascular endothelialcells (HGEC). Previously, we found that Eliglustat (EG), a Gb3 synthesisinhibitor, prevents the cytotoxic effects of Stx2 on HGEC. In this work, we evaluatedthe action of EG against the effects of Stx2 in vivo. Male BALB/c mice atweaning (17-21 days) received 3 doses of EG (0.6 mg/g body weight (bwt)administered intraperitoneally (i.p.) every 24 h. After a rest period of 5days, mice were i.p. injected with a lethal (1ng/g bwt) or sublethal (0.1 ng/gbwt) dose of Stx2 (EG+Stx2) or PBS (EG). Two additional groups of mice withoutEG pre-treatment were injected one with PBS (Ctrl) and another with Stx2(Stx2). Survival, body weight (Δ weight= body weight after Stx2 or PBS injection-bodyweight at a day before injection) and food intake were registered daily. EG didnot affect body weight gain (Δ weight: EG: 0.61 ± 0.07 g vs. Ctrl: 0.76 ± 0.09g; n=3, ns). After Stx2 lethal dose treatment, EG+Stx2 mice showed a bodyweight decrease and a survival time (48-72 h) similar to Stx2 mice. On thecontrary, after 3 days of Stx2 sublethal dose injection, while Stx2 miceexhibited piloerection and inactivity and body weight loss, EG+Stx2 mice did notshow signs of illness and gained weight (Δ weight: EG+Stx2: 0.81 ± 0.09 vs.Stx2: -0.65 ± 0.05 g; n=3, p<0.05). Body weight loss in Stx2 mice wasassociated with a significant decrease (70%) in food intake, unlike EGpre-treated mice that reduced intake by only 15% (n=3, p<0.05). Theseresults suggest that EG may reduce the disease symptoms caused by Stx2, such aspoor appetite and the resulting body weight loss. Future studies will analyzeif EG prevents the renal damage and will improve EG treatment to avoidmortality.
Fil: Gomez, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Toytoyndjian, Eugenia Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y LIII Reunión Anual de la Asociación Argentina de Fisiología
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Fisiología
description Typical HemolyticUremic Syndrome (HUS) is a complication of Shiga toxin (Stx)-producingEscherichia coli (STEC) infection and the most frequent cause of acute renalfailure in children in Argentina. Stx2 binds to globotriaosylceramide (Gb3)receptor and causes direct damage on human renal microvascular endothelialcells (HGEC). Previously, we found that Eliglustat (EG), a Gb3 synthesisinhibitor, prevents the cytotoxic effects of Stx2 on HGEC. In this work, we evaluatedthe action of EG against the effects of Stx2 in vivo. Male BALB/c mice atweaning (17-21 days) received 3 doses of EG (0.6 mg/g body weight (bwt)administered intraperitoneally (i.p.) every 24 h. After a rest period of 5days, mice were i.p. injected with a lethal (1ng/g bwt) or sublethal (0.1 ng/gbwt) dose of Stx2 (EG+Stx2) or PBS (EG). Two additional groups of mice withoutEG pre-treatment were injected one with PBS (Ctrl) and another with Stx2(Stx2). Survival, body weight (Δ weight= body weight after Stx2 or PBS injection-bodyweight at a day before injection) and food intake were registered daily. EG didnot affect body weight gain (Δ weight: EG: 0.61 ± 0.07 g vs. Ctrl: 0.76 ± 0.09g; n=3, ns). After Stx2 lethal dose treatment, EG+Stx2 mice showed a bodyweight decrease and a survival time (48-72 h) similar to Stx2 mice. On thecontrary, after 3 days of Stx2 sublethal dose injection, while Stx2 miceexhibited piloerection and inactivity and body weight loss, EG+Stx2 mice did notshow signs of illness and gained weight (Δ weight: EG+Stx2: 0.81 ± 0.09 vs.Stx2: -0.65 ± 0.05 g; n=3, p<0.05). Body weight loss in Stx2 mice wasassociated with a significant decrease (70%) in food intake, unlike EGpre-treated mice that reduced intake by only 15% (n=3, p<0.05). Theseresults suggest that EG may reduce the disease symptoms caused by Stx2, such aspoor appetite and the resulting body weight loss. Future studies will analyzeif EG prevents the renal damage and will improve EG treatment to avoidmortality.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/193264
Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y LIII Reunión Anual de la Asociación Argentina de Fisiología; Argentina; 2020; 84-84
0025-7680
CONICET Digital
CONICET
url http://hdl.handle.net/11336/193264
identifier_str_mv Eliglustat as a possible strategy to prevent the detrimental effects of Shiga toxin type 2: Preliminary results in vivo; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y LIII Reunión Anual de la Asociación Argentina de Fisiología; Argentina; 2020; 84-84
0025-7680
CONICET Digital
CONICET
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dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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