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Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats

OBJECTIVE: Antimalarials are globally used against plasmodium infections, however, information on the safety of new antimalarial combination therapies on the gastric mucosa is scarce. The aim of this study was to investigate the effects of Artesunate-Amodiaquine and Artemether-Lumefantrine on ulcer...

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Autores principales: Kalange, Muhamudu, Nansunga, Miriam, Kasozi, Keneth Iceland, Kasolo, Josephine, Namulema, Jackline, Atusiimirwe, Jovile Kasande, Ayikobua, Emanuel Tiyo, Ssempijja, Fred, Munanura, Edson Ireeta, Matama, Kevin, Semuyaba, Ibrahim, Zirintunda, Gerald, Okpanachi, Alfred Omachonu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178572/
https://www.ncbi.nlm.nih.gov/pubmed/32326975
http://dx.doi.org/10.1186/s13104-020-05073-7
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author Kalange, Muhamudu
Nansunga, Miriam
Kasozi, Keneth Iceland
Kasolo, Josephine
Namulema, Jackline
Atusiimirwe, Jovile Kasande
Ayikobua, Emanuel Tiyo
Ssempijja, Fred
Munanura, Edson Ireeta
Matama, Kevin
Semuyaba, Ibrahim
Zirintunda, Gerald
Okpanachi, Alfred Omachonu
author_facet Kalange, Muhamudu
Nansunga, Miriam
Kasozi, Keneth Iceland
Kasolo, Josephine
Namulema, Jackline
Atusiimirwe, Jovile Kasande
Ayikobua, Emanuel Tiyo
Ssempijja, Fred
Munanura, Edson Ireeta
Matama, Kevin
Semuyaba, Ibrahim
Zirintunda, Gerald
Okpanachi, Alfred Omachonu
author_sort Kalange, Muhamudu
collection PubMed
description OBJECTIVE: Antimalarials are globally used against plasmodium infections, however, information on the safety of new antimalarial combination therapies on the gastric mucosa is scarce. The aim of this study was to investigate the effects of Artesunate-Amodiaquine and Artemether-Lumefantrine on ulcer induction. Malondialdehyde (MDA), reduced glutathione (GSH) and major histological changes in male Wistar rats following ulcer induction using Indomethacin were investigated. Gastric ulcers were in four groups; Group I was administered Artesunate, group II received Artesunate-Amodiaquine, group III received Artemether-Lumefantrine, and group IV was a positive control (normal saline). Group V was the negative control consisting of healthy rats. RESULTS: Antimalarial combination therapies were associated with a high gastric ulcer index than a single antimalarial agent, Artesunate. In addition, levels of MDA were significantly higher in the combination of therapies while levels of GSH were lower in comparison to Artesunate and the negative control. Microscopically, antimalarial combination therapies were associated with severe inflammation and tissue damage than Artesunate in the gastric mucosa showing that antimalarial combination therapies exert their toxic effects through oxidative stress mechanisms, and this leads to cellular damage. Findings in this study demonstrate a need to revisit information on the pharmacodynamics of major circulating antimalarial agents in developing countries.
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spelling pubmed-71785722020-04-24 Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats Kalange, Muhamudu Nansunga, Miriam Kasozi, Keneth Iceland Kasolo, Josephine Namulema, Jackline Atusiimirwe, Jovile Kasande Ayikobua, Emanuel Tiyo Ssempijja, Fred Munanura, Edson Ireeta Matama, Kevin Semuyaba, Ibrahim Zirintunda, Gerald Okpanachi, Alfred Omachonu BMC Res Notes Research Note OBJECTIVE: Antimalarials are globally used against plasmodium infections, however, information on the safety of new antimalarial combination therapies on the gastric mucosa is scarce. The aim of this study was to investigate the effects of Artesunate-Amodiaquine and Artemether-Lumefantrine on ulcer induction. Malondialdehyde (MDA), reduced glutathione (GSH) and major histological changes in male Wistar rats following ulcer induction using Indomethacin were investigated. Gastric ulcers were in four groups; Group I was administered Artesunate, group II received Artesunate-Amodiaquine, group III received Artemether-Lumefantrine, and group IV was a positive control (normal saline). Group V was the negative control consisting of healthy rats. RESULTS: Antimalarial combination therapies were associated with a high gastric ulcer index than a single antimalarial agent, Artesunate. In addition, levels of MDA were significantly higher in the combination of therapies while levels of GSH were lower in comparison to Artesunate and the negative control. Microscopically, antimalarial combination therapies were associated with severe inflammation and tissue damage than Artesunate in the gastric mucosa showing that antimalarial combination therapies exert their toxic effects through oxidative stress mechanisms, and this leads to cellular damage. Findings in this study demonstrate a need to revisit information on the pharmacodynamics of major circulating antimalarial agents in developing countries. BioMed Central 2020-04-23 /pmc/articles/PMC7178572/ /pubmed/32326975 http://dx.doi.org/10.1186/s13104-020-05073-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Note
Kalange, Muhamudu
Nansunga, Miriam
Kasozi, Keneth Iceland
Kasolo, Josephine
Namulema, Jackline
Atusiimirwe, Jovile Kasande
Ayikobua, Emanuel Tiyo
Ssempijja, Fred
Munanura, Edson Ireeta
Matama, Kevin
Semuyaba, Ibrahim
Zirintunda, Gerald
Okpanachi, Alfred Omachonu
Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats
title Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats
title_full Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats
title_fullStr Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats
title_full_unstemmed Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats
title_short Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats
title_sort antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male wistar rats
topic Research Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178572/
https://www.ncbi.nlm.nih.gov/pubmed/32326975
http://dx.doi.org/10.1186/s13104-020-05073-7
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