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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-01969-x |
| _version_ | 1830414891460067328 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T20:53:50Z |
| format | Article |
| id | doaj.art-be1d8a9f27ec4e22b6204f40e7d6e1ae |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T20:53:50Z |
| publishDate | 2021-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-be1d8a9f27ec4e22b6204f40e7d6e1ae2022-12-21T19:26:52ZengNature PortfolioScientific Reports2045-23222021-12-0111111210.1038/s41598-021-01969-xLosartan improves intestinal mucositis induced by 5-fluorouracil in miceMaisie Mitchele Barbosa Oliveira0Aurigena Antunes de Araújo1Susana Barbosa Ribeiro2Polyana Crislayne Moreira de Sales Mota3Vitória Barros Marques4Conceição da Silva Martins Rebouças5Jozi Godoy Figueiredo6Patrícia Batista Barra7Gerly Anne de Castro Brito8Renata Ferreira de Carvalho Leitão9Gerlane Coelho Bernardo Guerra10Caroline Addison Carvalho Xavier de Medeiros11Post Graduate Program Biotechnology-RENORBIO, Federal University of Rio Grande do Norte (UFRN)Post Graduate Program in Pharmaceutical Science, Post Graduate Program Dental Sciences, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte (UFRN)Junior Postdoctoral Student CNPq-Federal University of Rio Grande do Norte (UFRN)Biosciences Center, Federal University of Rio Grande do Norte (UFRN)Biosciences Center, Federal University of Rio Grande do Norte (UFRN)Department of Morphology, Faculty of Medicine, Federal University of Ceará (UFC)Department of Biochemistry, Faculty of Vale do São Lourenço (EDUVALE)Post Graduate Program in Biology Teaching in National Network-PROFBIO, Department of Biomedical Sciences, State University of Rio Grande do Norte (UERN)Post Graduate Program Morphofunctional Sciences, Post Graduate Program Medical Sciences, Department of Morphology, Faculty of Medicine, Federal University of Ceará (UFC)Post Graduate Program Morphofunctional Sciences, Department of Morphology, Faculty of Medicine, Federal University of Ceará (UFC)Post Graduate Program Biochemistry and Molecular Biology, Post Graduate Program Pharmaceutical Science, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte (UFRN)Post Graduate Program Biotechnology-RENORBIO, Post Graduate Program Biochemistry and Molecular Biology, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte (UFRN)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.https://doi.org/10.1038/s41598-021-01969-x |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | Losartan improves intestinal mucositis induced by 5-fluorouracil in mice |
| title_sort | losartan improves intestinal mucositis induced by 5 fluorouracil in mice |
| url | https://doi.org/10.1038/s41598-021-01969-x |
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