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

Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research note Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats Muhamudu Kalange, Miriam Nansunga, Keneth Iceland Kasozi, Josephine Kasolo, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.22004/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Apr, 2020 Read the published version in BMC Research Notes → Version 1 posted 7 You are reading this latest preprint version Abstract 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 the study was to establish the effects of Artesunate-Amodiaquine and Artemether-Lumefantrine on gastric ulcers, malondialdehyde (MDA), reduced glutathione (GSH) and identify major histological changes in male Wistar rats. Gastric ulcers were induced using Indomethacin in four groups and group 1 was administered Artesunate, group 2 received Artesunate-Amodiaquine, group 3 received Artemether-Lumefantrine, and group 4 was a positive control (normal saline). Group five 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 apoptosis. Findings in this study demonstrate a new to revisit information on the pharmacodynamics of major circulating antimalarial agents in developing countries. Neurobiology of Disease Antimalarials Pharmacodynamics of antimalarial agents Malaria in developing countries Gastric ulcers Figures Figure 1 Figure 2 Full Text Supplementary Files ARRIVECHECKLIST.docx Cite Share Download PDF Status: Published Journal Publication published 23 Apr, 2020 Read the published version in BMC Research Notes → Version 1 posted Review # 1 received at journal 04 Apr, 2020 Editor assigned by journal 24 Jan, 2020 Reviewers invited by journal 24 Jan, 2020 Reviewer # 1 agreed at journal 24 Jan, 2020 First submitted to journal 23 Jan, 2020 Submission checks completed at journal 23 Jan, 2020 Editor invited by journal 23 Jan, 2020 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-12585","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research note","associatedPublications":[],"authors":[{"id":315248,"identity":"b14d3f26-b9de-4eba-a6e4-cf19218526a0","order_by":1,"name":"Muhamudu Kalange","email":"","orcid":"","institution":"Kampala International University - Western Campus","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Muhamudu","middleName":"","lastName":"Kalange","suffix":""},{"id":315249,"identity":"c903b4c9-c6f4-4484-bc7e-f534cf97ff7b","order_by":2,"name":"Miriam Nansunga","email":"","orcid":"","institution":"International Hospital Kampala","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Miriam","middleName":"","lastName":"Nansunga","suffix":""},{"id":315250,"identity":"b80e4a27-4068-4459-9f64-4f165a2436b5","order_by":3,"name":"Keneth Iceland Kasozi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYBACCWYg8YCBgbGBvQHIMrAgUksCSAvPAZAWCSK0MMC0SCTA+fiBZDvzwwcJNXdkN9x8fnXDjwIJBv727gS8WqSZ2YwNEo49M95wO6fsZg/QYRJnzm7Aq0WOmYdNIoHtcCJQS9oNHqAWA4lcglrYfyT8A2q5eSbt5h9itEgDbWFIbANqucF+7DZRtkg2sxlLJPYdNp55JofttoyBBA9Bv0icP/zww4dvh2X7jh9/dvPNHxs5/vZe/FrgQOEAjwGI5iFOOQjIN7A/IF71KBgFo2AUjCgAAL63S3s/U7xGAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-5763-7964","institution":"Kampala International University - 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Graphs A = Ulcer index, B = concentrations of malondialdehyde and C = concentrations of reduced glutathione.","description":"","filename":"Slide1.TIF","url":"https://assets-eu.researchsquare.com/files/48842a3c-2129-432e-80b3-a72847dd297c/v1/Slide1.TIF"},{"id":420661,"identity":"cae68b67-52b2-4f88-8b8e-38e2e02ffc24","added_by":"auto","created_at":"2020-01-28 21:06:25","extension":"tif","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":61018,"visible":true,"origin":"","legend":"Histological changes in gastric mucosa and epithelia following administration of 169 common antimalarials in male Wister rats. 1 = Gastric lumen; 2 = Gastric pit; 3 = Columnar 170\n8\nepithelium; 4 = Parietal cells; 5 = Chief cells; 6 = Lamina muscularis; 7 = Gastric glands; 8 = Sub mucosa; 9 = Endothelium of blood vessel; 10 = Blood cell; 11 = Vacoulations in nonglandular 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Notes","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Antimalarials, Pharmacodynamics of antimalarial agents, Malaria in developing countries, Gastric ulcers","lastPublishedDoi":"10.21203/rs.2.22004/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.22004/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective:\u0026nbsp;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 the study was to establish the effects of Artesunate-Amodiaquine and Artemether-Lumefantrine on gastric ulcers, malondialdehyde (MDA), reduced glutathione (GSH) and identify major histological changes in male Wistar rats. Gastric ulcers were induced using Indomethacin in four groups and group 1 was administered Artesunate, group 2 received Artesunate-Amodiaquine, group 3 received Artemether-Lumefantrine, and group 4 was a positive control (normal saline). Group five was the negative control consisting of healthy rats. \u003c/p\u003e\u003cp\u003eResults: 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 apoptosis. Findings in this study demonstrate a new to revisit information on the pharmacodynamics of major circulating antimalarial agents in developing countries.\u003c/p\u003e","manuscriptTitle":"Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-01-28 21:06:24","doi":"10.21203/rs.2.22004/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2020-04-04T12:00:00+00:00","index":1,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"editorAssigned","content":"","date":"2020-01-24T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-01-24T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-01-24T12:00:00+00:00","index":1,"fulltext":""},{"type":"submitted","content":"","date":"2020-01-23T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-01-23T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-01-23T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-research-notes","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"resn","sideBox":"Learn more about [BMC Research Notes](http://bmcresnotes.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/resn/default.aspx","title":"BMC Research Notes","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4e8849b8-87f2-4d7c-8da8-8724f9506a2e","owner":[],"postedDate":"January 28th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":53689,"name":"Neurobiology of Disease"}],"tags":[],"updatedAt":"2021-07-27T21:02:44+00:00","versionOfRecord":{"articleIdentity":"rs-12585","link":"https://doi.org/10.1186/s13104-020-05073-7","journal":{"identity":"bmc-research-notes","isVorOnly":false,"title":"BMC Research Notes"},"publishedOn":"2020-04-23 21:02:44","publishedOnDateReadable":"April 23rd, 2020"},"versionCreatedAt":"2020-01-28 21:06:24","video":"","vorDoi":"10.1186/s13104-020-05073-7","vorDoiUrl":"https://doi.org/10.1186/s13104-020-05073-7","workflowStages":[]},"version":"v1","identity":"rs-12585","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-12585","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}