{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:06:00Z","timestamp":1780376760840,"version":"3.54.1"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006701","name":"Umm Al-Qura University","doi-asserted-by":"publisher","award":["26UQU4330050GSSR03"],"award-info":[{"award-number":["26UQU4330050GSSR03"]}],"id":[{"id":"10.13039\/501100006701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006701","name":"Umm Al-Qura University","doi-asserted-by":"publisher","award":["26UQU4330050GSSR03"],"award-info":[{"award-number":["26UQU4330050GSSR03"]}],"id":[{"id":"10.13039\/501100006701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Giardia lamblia<\/jats:italic>\n                      infection (giardiasis) remains a significant global health concern, and the emergence of drug resistance to the first-line treatment, Metronidazole (MTZ), necessitates the exploration of alternative therapeutic agents. This study investigates the potential of Atorvastatin, as a repurposed drug for giardiasis, focusing on its direct antiparasitic activity and its role in modulating the associated inflammatory pathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Molecular docking simulations were performed to assess the binding affinity of Atorvastatin and MTZ against four key enzymes in the\n                      <jats:italic>G. lamblia<\/jats:italic>\n                      mevalonate pathway, which are farnesyl transferase (ftase), isopentenyl pyrophosphate isomerase (ipp), mevalonate diphosphate decarboxylase (mvd), and mevalonate kinase (mvk). An\n                      <jats:italic>in vivo<\/jats:italic>\n                      experimental model utilized Swiss albino mice infected with\n                      <jats:italic>G. lamblia<\/jats:italic>\n                      and treated with MTZ (120\u202fmg\/kg\/day for 7\u202fdays) or Atorvastatin (20\u202fmg\/kg\/day and 40\u202fmg\/kg\/day for 5\u202fdays) was used. Efficacy of treatments was evaluated by quantifying intestinal trophozoite counts. Furthermore, the study assessed liver function (ALT\/AST), intestinal and liver histopathology, and the expression of the inflammatory markers inducible Nitric Oxide Synthase (iNOS) and interleukin 6 (IL 6) in the intestinal tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Molecular docking revealed that Atorvastatin exhibited comparable or slightly superior binding affinities to the targeted\n                      <jats:italic>G. lamblia<\/jats:italic>\n                      enzymes compared to MTZ, with the strongest interaction observed with ipp_v6th89 (\u22125.7\u202fkcal\/mol).\n                      <jats:italic>In vivo<\/jats:italic>\n                      , Atorvastatin demonstrated significant, dose-dependent antiparasitic activity, achieving a 41.54% reduction in trophozoite counts at 40\u202fmg\/kg, though this was lower than the 71.73% reduction achieved by MTZ. Crucially, Atorvastatin exhibited a superior anti-inflammatory effect. The higher dose of Atorvastatin suppressed iNOS expression to 5.40% of the reaction area, a nearly four-fold reduction compared to the infected untreated group (19.59%) and significantly better than the modest reduction seen with MTZ (17.49%). On the other hand, Atorvastatin (at a dose of 40\u202fmg \/kg) proved to be the most potent intervention, suppressing IL-6 expression to a low average of 6.12% in comparison to 26.7 and 17.6% reaction area for infected untreated and MTZ treated mice, respectively. Histopathological analysis confirmed that Atorvastatin treatment effectively restored intestinal architecture and mitigated liver pathology, correlating with a significant reduction in elevated serum ALT levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Atorvastatin possesses a dual therapeutic role against giardiasis. It acts as a moderate antiparasitic agent, likely by targeting the mevalonate pathway, and as a potent immunomodulatory agent. Its superior ability to suppress the inflammatory response and mitigate intestinal and hepatic pathology suggests that Atorvastatin is a promising candidate for an adjunct therapy to Metronidazole, particularly in cases where inflammation and chronic sequelae are major concerns.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1788316","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:29:01Z","timestamp":1780374541000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The therapeutic potential of atorvastatin in treatment of G. lamblia infected mice; in silico, parasitological, and histopathological study"],"prefix":"10.3389","volume":"13","author":[{"given":"Khalil","family":"Mohamed","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Medical Statistics, Faculty of Public Health and Health Informatics, Umm Al-Qura University","place":["Mecca, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marawan","family":"Khodary","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Qena University","place":["Qena, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"hamed","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Qena University","place":["Qena, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Alhazmi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Medical Statistics, Faculty of Public Health and Health Informatics, Umm Al-Qura University","place":["Mecca, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hattan S.","family":"Gattan","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]},{"name":"Special Infectious Agents Unit, King Fahad Medical Research Center, King AbdulAziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed H.","family":"Alruhaili","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit, King Fahad Medical Research Center, King AbdulAziz University","place":["Jeddah, Saudi Arabia"]},{"name":"Department of Clinical Microbiology and Immunology, Faculty of Medicine, King AbdulAziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman Fathi","family":"Fadel","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Sohag University","place":["Sohag, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem A.","family":"Elshabrawy","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, College of Osteopathic Medicine, Sam Houston State University","place":["Conroe, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa M.","family":"El-kady","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Qena University","place":["Qena, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"817468","DOI":"10.3389\/fimmu.2022.817468","article-title":"Mucosal defense against Giardia at the intestinal epithelial cell Interface","volume":"13","author":"Solaymani-Mohammadi","year":"2022","journal-title":"Front Immunol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.pt.2006.02.015","article-title":"Giardia 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