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The Alpha-Lipoic Acid Improves Survival and Prevents Irinotecan-Induced Inflammation and Intestinal Dysmotility in Mice

Irinotecan, an anticancer drug, induces diarrhea and intestinal inflammation, resulting in an increase in the cost of care and in treatment delays. In this study, we investigated whether alpha-lipoic acid (α-LA) could improve irinotecan-mediated intestinal inflammation, diarrhea and dysmotility. Int...

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Autores principales: Costa, Daniely V. S., Costa, Deiziane V. S., Sousa, Caren N. S., Silva, Angeline M. H. P., Medeiros, Ingridy S., Martins, Dainesy S., Martins, Conceição S., Pequeno, Ana L. V., Lima-Júnior, Roberto C. P., Soares, Pedro M. G., Vasconcelos, Silvânia M. M., Brito, Gerly A. C., Souza, Emmanuel P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692584/
https://www.ncbi.nlm.nih.gov/pubmed/33152996
http://dx.doi.org/10.3390/ph13110361
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author Costa, Daniely V. S.
Costa, Deiziane V. S.
Sousa, Caren N. S.
Silva, Angeline M. H. P.
Medeiros, Ingridy S.
Martins, Dainesy S.
Martins, Conceição S.
Pequeno, Ana L. V.
Lima-Júnior, Roberto C. P.
Soares, Pedro M. G.
Vasconcelos, Silvânia M. M.
Brito, Gerly A. C.
Souza, Emmanuel P.
author_facet Costa, Daniely V. S.
Costa, Deiziane V. S.
Sousa, Caren N. S.
Silva, Angeline M. H. P.
Medeiros, Ingridy S.
Martins, Dainesy S.
Martins, Conceição S.
Pequeno, Ana L. V.
Lima-Júnior, Roberto C. P.
Soares, Pedro M. G.
Vasconcelos, Silvânia M. M.
Brito, Gerly A. C.
Souza, Emmanuel P.
author_sort Costa, Daniely V. S.
collection PubMed
description Irinotecan, an anticancer drug, induces diarrhea and intestinal inflammation, resulting in an increase in the cost of care and in treatment delays. In this study, we investigated whether alpha-lipoic acid (α-LA) could improve irinotecan-mediated intestinal inflammation, diarrhea and dysmotility. Intestinal mucositis was induced by irinotecan injection (75 mg/kg, i.p., for 4 days) in Swiss mice. α-LA (50, 100 or 200 mg/kg, gavage) was administered daily 1 h before the injection of irinotecan. Duodenum tissues were obtained for inflammation and proliferation analysis. The outcomes: diarrhea, intestinal dysmotility, weight body loss and survival were evaluated. Compared with the control condition, irinotecan diminished (p < 0.05) intestinal villus height, caused a loss of crypt integrity and intense inflammatory cell infiltration, increased myeloperoxidase (MPO), IL-6 and IL-1β levels and decreased reduced glutathione (GSH) levels in duodenum segments and increased gastric retention and decreased liquid retention in the medial intestinal segment, resulting in increased intestinal transit, severe diarrhea and reduced survival (approximately 72%). Furthermore, α-LA (200 mg/kg) pretreatment ameliorated (p < 0.05) these irinotecan-induced effects. Our findings show that α-LA reduced irinotecan-induced inflammation, intestinal dysmotility and diarrhea, resulting in improved survival. α-LA may be a useful therapeutic agent for the treatment of gut dysmotility in patients with intestinal mucositis associated with irinotecan treatment.
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spelling pubmed-76925842020-11-28 The Alpha-Lipoic Acid Improves Survival and Prevents Irinotecan-Induced Inflammation and Intestinal Dysmotility in Mice Costa, Daniely V. S. Costa, Deiziane V. S. Sousa, Caren N. S. Silva, Angeline M. H. P. Medeiros, Ingridy S. Martins, Dainesy S. Martins, Conceição S. Pequeno, Ana L. V. Lima-Júnior, Roberto C. P. Soares, Pedro M. G. Vasconcelos, Silvânia M. M. Brito, Gerly A. C. Souza, Emmanuel P. Pharmaceuticals (Basel) Article Irinotecan, an anticancer drug, induces diarrhea and intestinal inflammation, resulting in an increase in the cost of care and in treatment delays. In this study, we investigated whether alpha-lipoic acid (α-LA) could improve irinotecan-mediated intestinal inflammation, diarrhea and dysmotility. Intestinal mucositis was induced by irinotecan injection (75 mg/kg, i.p., for 4 days) in Swiss mice. α-LA (50, 100 or 200 mg/kg, gavage) was administered daily 1 h before the injection of irinotecan. Duodenum tissues were obtained for inflammation and proliferation analysis. The outcomes: diarrhea, intestinal dysmotility, weight body loss and survival were evaluated. Compared with the control condition, irinotecan diminished (p < 0.05) intestinal villus height, caused a loss of crypt integrity and intense inflammatory cell infiltration, increased myeloperoxidase (MPO), IL-6 and IL-1β levels and decreased reduced glutathione (GSH) levels in duodenum segments and increased gastric retention and decreased liquid retention in the medial intestinal segment, resulting in increased intestinal transit, severe diarrhea and reduced survival (approximately 72%). Furthermore, α-LA (200 mg/kg) pretreatment ameliorated (p < 0.05) these irinotecan-induced effects. Our findings show that α-LA reduced irinotecan-induced inflammation, intestinal dysmotility and diarrhea, resulting in improved survival. α-LA may be a useful therapeutic agent for the treatment of gut dysmotility in patients with intestinal mucositis associated with irinotecan treatment. MDPI 2020-11-03 /pmc/articles/PMC7692584/ /pubmed/33152996 http://dx.doi.org/10.3390/ph13110361 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Costa, Daniely V. S.
Costa, Deiziane V. S.
Sousa, Caren N. S.
Silva, Angeline M. H. P.
Medeiros, Ingridy S.
Martins, Dainesy S.
Martins, Conceição S.
Pequeno, Ana L. V.
Lima-Júnior, Roberto C. P.
Soares, Pedro M. G.
Vasconcelos, Silvânia M. M.
Brito, Gerly A. C.
Souza, Emmanuel P.
The Alpha-Lipoic Acid Improves Survival and Prevents Irinotecan-Induced Inflammation and Intestinal Dysmotility in Mice
title The Alpha-Lipoic Acid Improves Survival and Prevents Irinotecan-Induced Inflammation and Intestinal Dysmotility in Mice
title_full The Alpha-Lipoic Acid Improves Survival and Prevents Irinotecan-Induced Inflammation and Intestinal Dysmotility in Mice
title_fullStr The Alpha-Lipoic Acid Improves Survival and Prevents Irinotecan-Induced Inflammation and Intestinal Dysmotility in Mice
title_full_unstemmed The Alpha-Lipoic Acid Improves Survival and Prevents Irinotecan-Induced Inflammation and Intestinal Dysmotility in Mice
title_short The Alpha-Lipoic Acid Improves Survival and Prevents Irinotecan-Induced Inflammation and Intestinal Dysmotility in Mice
title_sort alpha-lipoic acid improves survival and prevents irinotecan-induced inflammation and intestinal dysmotility in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692584/
https://www.ncbi.nlm.nih.gov/pubmed/33152996
http://dx.doi.org/10.3390/ph13110361
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