Losartan improves intestinal mucositis induced by 5-fluorouracil in mice

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 min...

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Bibliographic Details
Published in:	Scientific reports Vol. 11; no. 1; p. 23241
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-12-2021 Nature Publishing Group Nature Portfolio
Subjects:	5-Fluorouracil 631/45 631/67 692/4020 692/4028 Angiotensin AT1 receptors Angiotensin II Angiotensin II Type 1 Receptor Blockers - pharmacology Animals Antimetabolites, Antineoplastic - adverse effects Chemotherapy Cytokines Cytokines - metabolism Female Fluorouracil - adverse effects Humanities and Social Sciences Inflammation Inflammation - drug therapy Intestinal Mucosa - pathology Leukopenia Losartan - pharmacology Mice Morphometry Mucosa Mucositis Mucositis - chemically induced Mucositis - drug therapy multidisciplinary NF-κB protein Oral administration Oxidative stress Oxidative Stress - drug effects Science Science (multidisciplinary) Small intestine Villus
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-021-01969-x