Losartan improves intestinal mucositis induced by 5-fluorouracil in mice

Abstract Intestinal mucositis (IM) is a common side effect of 5-fluorouracil (5-FU)-based chemotherapy, which negatively impacts therapeutic outcomes and delays subsequent cycles of chemotherapy resulting in dose reductions and treatment discontinuation. In search of new pharmacological alternatives...

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Autores principales:	Maisie Mitchele Barbosa Oliveira, Aurigena Antunes de Araújo, Susana Barbosa Ribeiro, Polyana Crislayne Moreira de Sales Mota, Vitória Barros Marques, Conceição da Silva Martins Rebouças, Jozi Godoy Figueiredo, Patrícia Batista Barra, Gerly Anne de Castro Brito, Renata Ferreira de Carvalho Leitão, Gerlane Coelho Bernardo Guerra, Caroline Addison Carvalho Xavier de Medeiros
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/be1d8a9f27ec4e22b6204f40e7d6e1ae
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spelling	oai:doaj.org-article:be1d8a9f27ec4e22b6204f40e7d6e1ae2021-12-05T12:13:01ZLosartan improves intestinal mucositis induced by 5-fluorouracil in mice10.1038/s41598-021-01969-x2045-2322https://doaj.org/article/be1d8a9f27ec4e22b6204f40e7d6e1ae2021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01969-xhttps://doaj.org/toc/2045-2322Abstract Intestinal mucositis (IM) is a common side effect of 5-fluorouracil (5-FU)-based chemotherapy, which negatively impacts therapeutic outcomes and delays subsequent cycles of chemotherapy resulting in dose reductions and treatment discontinuation. In search of new pharmacological alternatives that minimize your symptoms, this work set out to study the effect of losartan (LOS), a receptor type I (AT1) angiotensin II antagonist, on intestinal mucositis induced by 5-FU. Intestinal mucositis was induced by a single intraperitoneal administration of 5-FU (450 mg/kg) in Swiss mice. Losartan (5, 25 or 50 mg/kg) or saline was orally administered 30 min before 5-FU and daily for 4 days. On 4th day, the animals were euthanized and segments of small intestine were collected to evaluate histopathological alterations (morphometric analysis), concentration of inflammatory cytokines, oxidative stress markers and genic expression of NF-κB p65, Fn-14 and TWEAK. Weight evaluation and changes in leukogram were also analyzed. 5-FU induced intense weight loss, leukopenia and reduction in villus height compared to saline group. Losartan (50 mg/kg) prevented 5-FU-induced inflammation by decreasing in the analyzed parameters compared to the 5-FU group. Our findings suggest that 50 mg/kg of losartan prevents the effects of 5-FU on intestinal mucosa in mice.Maisie Mitchele Barbosa OliveiraAurigena Antunes de AraújoSusana Barbosa RibeiroPolyana Crislayne Moreira de Sales MotaVitória Barros MarquesConceição da Silva Martins RebouçasJozi Godoy FigueiredoPatrícia Batista BarraGerly Anne de Castro BritoRenata Ferreira de Carvalho LeitãoGerlane Coelho Bernardo GuerraCaroline Addison Carvalho Xavier de MedeirosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maisie Mitchele Barbosa Oliveira Aurigena Antunes de Araújo Susana Barbosa Ribeiro Polyana Crislayne Moreira de Sales Mota Vitória Barros Marques Conceição da Silva Martins Rebouças Jozi Godoy Figueiredo Patrícia Batista Barra Gerly Anne de Castro Brito Renata Ferreira de Carvalho Leitão Gerlane Coelho Bernardo Guerra Caroline Addison Carvalho Xavier de Medeiros Losartan improves intestinal mucositis induced by 5-fluorouracil in mice
description	Abstract Intestinal mucositis (IM) is a common side effect of 5-fluorouracil (5-FU)-based chemotherapy, which negatively impacts therapeutic outcomes and delays subsequent cycles of chemotherapy resulting in dose reductions and treatment discontinuation. In search of new pharmacological alternatives that minimize your symptoms, this work set out to study the effect of losartan (LOS), a receptor type I (AT1) angiotensin II antagonist, on intestinal mucositis induced by 5-FU. Intestinal mucositis was induced by a single intraperitoneal administration of 5-FU (450 mg/kg) in Swiss mice. Losartan (5, 25 or 50 mg/kg) or saline was orally administered 30 min before 5-FU and daily for 4 days. On 4th day, the animals were euthanized and segments of small intestine were collected to evaluate histopathological alterations (morphometric analysis), concentration of inflammatory cytokines, oxidative stress markers and genic expression of NF-κB p65, Fn-14 and TWEAK. Weight evaluation and changes in leukogram were also analyzed. 5-FU induced intense weight loss, leukopenia and reduction in villus height compared to saline group. Losartan (50 mg/kg) prevented 5-FU-induced inflammation by decreasing in the analyzed parameters compared to the 5-FU group. Our findings suggest that 50 mg/kg of losartan prevents the effects of 5-FU on intestinal mucosa in mice.
format	article
author	Maisie Mitchele Barbosa Oliveira Aurigena Antunes de Araújo Susana Barbosa Ribeiro Polyana Crislayne Moreira de Sales Mota Vitória Barros Marques Conceição da Silva Martins Rebouças Jozi Godoy Figueiredo Patrícia Batista Barra Gerly Anne de Castro Brito Renata Ferreira de Carvalho Leitão Gerlane Coelho Bernardo Guerra Caroline Addison Carvalho Xavier de Medeiros
author_facet	Maisie Mitchele Barbosa Oliveira Aurigena Antunes de Araújo Susana Barbosa Ribeiro Polyana Crislayne Moreira de Sales Mota Vitória Barros Marques Conceição da Silva Martins Rebouças Jozi Godoy Figueiredo Patrícia Batista Barra Gerly Anne de Castro Brito Renata Ferreira de Carvalho Leitão Gerlane Coelho Bernardo Guerra Caroline Addison Carvalho Xavier de Medeiros
author_sort	Maisie Mitchele Barbosa Oliveira
title	Losartan improves intestinal mucositis induced by 5-fluorouracil in mice
title_short	Losartan improves intestinal mucositis induced by 5-fluorouracil in mice
title_full	Losartan improves intestinal mucositis induced by 5-fluorouracil in mice
title_fullStr	Losartan improves intestinal mucositis induced by 5-fluorouracil in mice
title_full_unstemmed	Losartan improves intestinal mucositis induced by 5-fluorouracil in mice
title_sort	losartan improves intestinal mucositis induced by 5-fluorouracil in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/be1d8a9f27ec4e22b6204f40e7d6e1ae
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Losartan improves intestinal mucositis induced by 5-fluorouracil in mice

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