Author:
Oliveira Maisie Mitchele Barbosa,de Araújo Aurigena Antunes,Ribeiro Susana Barbosa,de Sales Mota Polyana Crislayne Moreira,Marques Vitória Barros,da Silva Martins Rebouças Conceição,Figueiredo Jozi Godoy,Barra Patrícia Batista,de Castro Brito Gerly Anne,de Carvalho Leitão Renata Ferreira,Guerra Gerlane Coelho Bernardo,de Medeiros Caroline Addison Carvalho Xavier
Abstract
AbstractIntestinal 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.
Funder
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brazil (CAPES)–Finance Code 001
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Publisher
Springer Science and Business Media LLC
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