Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables

Autores
Prado, Natalia Jorgelina; Ramirez, Daniela Andrea; Mazzei, Luciana Jorgelina; Parra, Micaela; Casarotto, Mariana; Calvo, Juan Pablo; Cuello Carrión, Fernando Darío; Ponce Zumino, Amira Zulma; Diez, Emiliano Raúl; Camargo, Alejandra Beatriz; Manucha, Walter Ariel Fernando
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Cardiovascular inflammation and oxidative stress are determining factors in high blood pressure and arrhythmias. Indole-3-carbinol is a cruciferous-derived phytochemical with potential anti-inflammatory and antioxidant effects. However, its implications on the modulation of cardiovascular inflammatory-oxidative markers are unknown. Objectives: To establish the effects of indole-3-carbinol on the oxidative-inflammatory-proarrhythmic conditions associated with hypertension. Materials: Histological, biochemical, molecular, and functional aspects were evaluated in 1) Culture of mouse BV-2 glial cells subjected to oxidative-inflammatory damage by lipopolysaccharides (100 ng/mL) in the presence or absence of 40 μM indole-3-carbinol (n = 5); 2) Male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats receiving indole-3-carbinol (2000 ppm/day, orally) during the first 8 weeks of life (n = 15); 3) Isolated rat hearts were submitted to 10 min regional ischemia and 10 min reperfusion. Results: 1) lipopolysaccharides induced oxidative stress and increased inflammatory markers; indole-3-carbinol reversed both conditions (interleukin 6, tumor necrosis factor α, the activity of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide, inducible nitric oxide synthase, heat shock protein 70, all p < 0.01 vs lipopolysaccharides). 2) SHR rats showed histological, structural, and functional changes with increasing systolic blood pressure (154 ± 8 mmHg vs. 122 ± 7 mmHg in Wistar Kyoto rats, p < 0.01); Inflammatory-oxidative markers also increased, and nitric oxide and heat shock protein 70 decreased. Conversely, indole-3-carbinol reduced oxidative-inflammatory markers and systolic blood pressure (133 ± 8 mmHg, p < 0.01 vs. SHR). 3) indole-3-carbinol reduced reperfusion arrhythmias from 8/10 in SHR to 0/10 (p = 0.0007 by Fisher's exact test). Conclusions: Indole-3-carbinol reduces the inflammatory-oxidative-proarrhythmic process of hypertension. The nitric oxide and heat shock protein 70 are relevant mechanisms of indole-3-carbinol protective actions. Further studies with this pleiotropic phytochemical as a promising cardioprotective are guaranteed.
Fil: Prado, Natalia Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ramirez, Daniela Andrea. Laboratorio de Cromatografía Para Agroalimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; Argentina
Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Parra, Micaela. Universidad Nacional de Cuyo; Argentina
Fil: Casarotto, Mariana. Universidad Nacional de Cuyo; Argentina
Fil: Calvo, Juan Pablo. Universidad Nacional de Cuyo; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ponce Zumino, Amira Zulma. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Camargo, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; Argentina
Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad del Aconcagua. Facultad de Ciencias Médicas; Argentina
Materia
ARRHYTHMIAS
HSP70
HYPERTENSION
INDOLE-3-CARBINOL
INFLAMMATION
OXIDATIVE STRESS
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:11336/197188

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetablesPrado, Natalia JorgelinaRamirez, Daniela AndreaMazzei, Luciana JorgelinaParra, MicaelaCasarotto, MarianaCalvo, Juan PabloCuello Carrión, Fernando DaríoPonce Zumino, Amira ZulmaDiez, Emiliano RaúlCamargo, Alejandra BeatrizManucha, Walter Ariel FernandoARRHYTHMIASHSP70HYPERTENSIONINDOLE-3-CARBINOLINFLAMMATIONOXIDATIVE STRESShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Cardiovascular inflammation and oxidative stress are determining factors in high blood pressure and arrhythmias. Indole-3-carbinol is a cruciferous-derived phytochemical with potential anti-inflammatory and antioxidant effects. However, its implications on the modulation of cardiovascular inflammatory-oxidative markers are unknown. Objectives: To establish the effects of indole-3-carbinol on the oxidative-inflammatory-proarrhythmic conditions associated with hypertension. Materials: Histological, biochemical, molecular, and functional aspects were evaluated in 1) Culture of mouse BV-2 glial cells subjected to oxidative-inflammatory damage by lipopolysaccharides (100 ng/mL) in the presence or absence of 40 μM indole-3-carbinol (n = 5); 2) Male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats receiving indole-3-carbinol (2000 ppm/day, orally) during the first 8 weeks of life (n = 15); 3) Isolated rat hearts were submitted to 10 min regional ischemia and 10 min reperfusion. Results: 1) lipopolysaccharides induced oxidative stress and increased inflammatory markers; indole-3-carbinol reversed both conditions (interleukin 6, tumor necrosis factor α, the activity of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide, inducible nitric oxide synthase, heat shock protein 70, all p < 0.01 vs lipopolysaccharides). 2) SHR rats showed histological, structural, and functional changes with increasing systolic blood pressure (154 ± 8 mmHg vs. 122 ± 7 mmHg in Wistar Kyoto rats, p < 0.01); Inflammatory-oxidative markers also increased, and nitric oxide and heat shock protein 70 decreased. Conversely, indole-3-carbinol reduced oxidative-inflammatory markers and systolic blood pressure (133 ± 8 mmHg, p < 0.01 vs. SHR). 3) indole-3-carbinol reduced reperfusion arrhythmias from 8/10 in SHR to 0/10 (p = 0.0007 by Fisher's exact test). Conclusions: Indole-3-carbinol reduces the inflammatory-oxidative-proarrhythmic process of hypertension. The nitric oxide and heat shock protein 70 are relevant mechanisms of indole-3-carbinol protective actions. Further studies with this pleiotropic phytochemical as a promising cardioprotective are guaranteed.Fil: Prado, Natalia Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ramirez, Daniela Andrea. Laboratorio de Cromatografía Para Agroalimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Parra, Micaela. Universidad Nacional de Cuyo; ArgentinaFil: Casarotto, Mariana. Universidad Nacional de Cuyo; ArgentinaFil: Calvo, Juan Pablo. Universidad Nacional de Cuyo; ArgentinaFil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ponce Zumino, Amira Zulma. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Camargo, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad del Aconcagua. Facultad de Ciencias Médicas; ArgentinaElsevier2022-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/197188Prado, Natalia Jorgelina; Ramirez, Daniela Andrea; Mazzei, Luciana Jorgelina; Parra, Micaela; Casarotto, Mariana; et al.; Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables; Elsevier; Heliyon; 8; 2; 2-2022; 1-82405-8440CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2405844022002778info:eu-repo/semantics/altIdentifier/doi/10.1016/j.heliyon.2022.e08989info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:24:19Zoai:ri.conicet.gov.ar:11336/197188instacron: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:34982025-09-29 10:24:19.29CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables
title Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables
spellingShingle Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables
Prado, Natalia Jorgelina
ARRHYTHMIAS
HSP70
HYPERTENSION
INDOLE-3-CARBINOL
INFLAMMATION
OXIDATIVE STRESS
title_short Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables
title_full Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables
title_fullStr Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables
title_full_unstemmed Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables
title_sort Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables
dc.creator.none.fl_str_mv Prado, Natalia Jorgelina
Ramirez, Daniela Andrea
Mazzei, Luciana Jorgelina
Parra, Micaela
Casarotto, Mariana
Calvo, Juan Pablo
Cuello Carrión, Fernando Darío
Ponce Zumino, Amira Zulma
Diez, Emiliano Raúl
Camargo, Alejandra Beatriz
Manucha, Walter Ariel Fernando
author Prado, Natalia Jorgelina
author_facet Prado, Natalia Jorgelina
Ramirez, Daniela Andrea
Mazzei, Luciana Jorgelina
Parra, Micaela
Casarotto, Mariana
Calvo, Juan Pablo
Cuello Carrión, Fernando Darío
Ponce Zumino, Amira Zulma
Diez, Emiliano Raúl
Camargo, Alejandra Beatriz
Manucha, Walter Ariel Fernando
author_role author
author2 Ramirez, Daniela Andrea
Mazzei, Luciana Jorgelina
Parra, Micaela
Casarotto, Mariana
Calvo, Juan Pablo
Cuello Carrión, Fernando Darío
Ponce Zumino, Amira Zulma
Diez, Emiliano Raúl
Camargo, Alejandra Beatriz
Manucha, Walter Ariel Fernando
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ARRHYTHMIAS
HSP70
HYPERTENSION
INDOLE-3-CARBINOL
INFLAMMATION
OXIDATIVE STRESS
topic ARRHYTHMIAS
HSP70
HYPERTENSION
INDOLE-3-CARBINOL
INFLAMMATION
OXIDATIVE STRESS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Cardiovascular inflammation and oxidative stress are determining factors in high blood pressure and arrhythmias. Indole-3-carbinol is a cruciferous-derived phytochemical with potential anti-inflammatory and antioxidant effects. However, its implications on the modulation of cardiovascular inflammatory-oxidative markers are unknown. Objectives: To establish the effects of indole-3-carbinol on the oxidative-inflammatory-proarrhythmic conditions associated with hypertension. Materials: Histological, biochemical, molecular, and functional aspects were evaluated in 1) Culture of mouse BV-2 glial cells subjected to oxidative-inflammatory damage by lipopolysaccharides (100 ng/mL) in the presence or absence of 40 μM indole-3-carbinol (n = 5); 2) Male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats receiving indole-3-carbinol (2000 ppm/day, orally) during the first 8 weeks of life (n = 15); 3) Isolated rat hearts were submitted to 10 min regional ischemia and 10 min reperfusion. Results: 1) lipopolysaccharides induced oxidative stress and increased inflammatory markers; indole-3-carbinol reversed both conditions (interleukin 6, tumor necrosis factor α, the activity of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide, inducible nitric oxide synthase, heat shock protein 70, all p < 0.01 vs lipopolysaccharides). 2) SHR rats showed histological, structural, and functional changes with increasing systolic blood pressure (154 ± 8 mmHg vs. 122 ± 7 mmHg in Wistar Kyoto rats, p < 0.01); Inflammatory-oxidative markers also increased, and nitric oxide and heat shock protein 70 decreased. Conversely, indole-3-carbinol reduced oxidative-inflammatory markers and systolic blood pressure (133 ± 8 mmHg, p < 0.01 vs. SHR). 3) indole-3-carbinol reduced reperfusion arrhythmias from 8/10 in SHR to 0/10 (p = 0.0007 by Fisher's exact test). Conclusions: Indole-3-carbinol reduces the inflammatory-oxidative-proarrhythmic process of hypertension. The nitric oxide and heat shock protein 70 are relevant mechanisms of indole-3-carbinol protective actions. Further studies with this pleiotropic phytochemical as a promising cardioprotective are guaranteed.
Fil: Prado, Natalia Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ramirez, Daniela Andrea. Laboratorio de Cromatografía Para Agroalimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; Argentina
Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Parra, Micaela. Universidad Nacional de Cuyo; Argentina
Fil: Casarotto, Mariana. Universidad Nacional de Cuyo; Argentina
Fil: Calvo, Juan Pablo. Universidad Nacional de Cuyo; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ponce Zumino, Amira Zulma. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Camargo, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; Argentina
Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad del Aconcagua. Facultad de Ciencias Médicas; Argentina
description Background: Cardiovascular inflammation and oxidative stress are determining factors in high blood pressure and arrhythmias. Indole-3-carbinol is a cruciferous-derived phytochemical with potential anti-inflammatory and antioxidant effects. However, its implications on the modulation of cardiovascular inflammatory-oxidative markers are unknown. Objectives: To establish the effects of indole-3-carbinol on the oxidative-inflammatory-proarrhythmic conditions associated with hypertension. Materials: Histological, biochemical, molecular, and functional aspects were evaluated in 1) Culture of mouse BV-2 glial cells subjected to oxidative-inflammatory damage by lipopolysaccharides (100 ng/mL) in the presence or absence of 40 μM indole-3-carbinol (n = 5); 2) Male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats receiving indole-3-carbinol (2000 ppm/day, orally) during the first 8 weeks of life (n = 15); 3) Isolated rat hearts were submitted to 10 min regional ischemia and 10 min reperfusion. Results: 1) lipopolysaccharides induced oxidative stress and increased inflammatory markers; indole-3-carbinol reversed both conditions (interleukin 6, tumor necrosis factor α, the activity of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide, inducible nitric oxide synthase, heat shock protein 70, all p < 0.01 vs lipopolysaccharides). 2) SHR rats showed histological, structural, and functional changes with increasing systolic blood pressure (154 ± 8 mmHg vs. 122 ± 7 mmHg in Wistar Kyoto rats, p < 0.01); Inflammatory-oxidative markers also increased, and nitric oxide and heat shock protein 70 decreased. Conversely, indole-3-carbinol reduced oxidative-inflammatory markers and systolic blood pressure (133 ± 8 mmHg, p < 0.01 vs. SHR). 3) indole-3-carbinol reduced reperfusion arrhythmias from 8/10 in SHR to 0/10 (p = 0.0007 by Fisher's exact test). Conclusions: Indole-3-carbinol reduces the inflammatory-oxidative-proarrhythmic process of hypertension. The nitric oxide and heat shock protein 70 are relevant mechanisms of indole-3-carbinol protective actions. Further studies with this pleiotropic phytochemical as a promising cardioprotective are guaranteed.
publishDate 2022
dc.date.none.fl_str_mv 2022-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/197188
Prado, Natalia Jorgelina; Ramirez, Daniela Andrea; Mazzei, Luciana Jorgelina; Parra, Micaela; Casarotto, Mariana; et al.; Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables; Elsevier; Heliyon; 8; 2; 2-2022; 1-8
2405-8440
CONICET Digital
CONICET
url http://hdl.handle.net/11336/197188
identifier_str_mv Prado, Natalia Jorgelina; Ramirez, Daniela Andrea; Mazzei, Luciana Jorgelina; Parra, Micaela; Casarotto, Mariana; et al.; Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables; Elsevier; Heliyon; 8; 2; 2-2022; 1-8
2405-8440
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.heliyon.2022.e08989
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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publisher.none.fl_str_mv Elsevier
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