[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-217177-en":3,"doc-seo-217177-105":30,"detail-sidebar-cat-0-en-105":96},{"code":4,"msg":5,"data":6},0,"success",{"doc_id":7,"user_id":8,"nickname":9,"user_avatar":10,"doc_module":4,"category_id":11,"category_name":12,"doc_title":13,"doc_description":14,"doc_content":15,"file_id":16,"file_url":17,"file_type":18,"file_size":19,"view_count":20,"is_deleted":4,"is_public":20,"is_downloadable":20,"audit_status":20,"page_count":21,"language":22,"language_code":23,"site_id":24,"html_lang":23,"table_of_contents":25,"faqs":26,"seo_title":27,"seo_description":14,"update_tm":28,"read_time":29},217177,1374404737137,"Adam","https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d",7,"Healthcare","Antileishmanial activity of tamoxifen - Study objectives, methods, results and conclusions","Tamoxifen is investigated for antileishmanial activity against Leishmania in vitro and in infected macrophage cultures. Drug effects are measured using cell counting and MTT cleavage for promastigotes and amastigotes, while intracellular parasite numbers are assessed in macrophages. Intravacuolar pH changes within parasitophorous vacuoles are monitored using fluorescent probes SNAFL-calcein and Acridine Orange. Tamoxifen shows potent killing across multiple species and increases activity when host vacuolar pH is alkalinized.","Journal of Antimicrobial Chemotherapy (2007) 60, 526–534 doi:10.1093/jac/dkm219  \nAdvance Access publication 21 June 2007  \nTamoxifen is effective against Leishmania and induces a rapid alkalinization of parasitophorous vacuoles harbouring Leishmania (Leishmania) amazonensis amastigotes  \nDanilo C. Miguel1, Jenicer K. U. Yokoyama-Yasunaka1, Walter K. Andreoli2, Renato A. Mortara2  \nand Silvia R. B. Uliana1*  \n1Departamento de Parasitologia, Instituto de Ciˆencias Biom´edicas, Universidade de S˜ao Paulo, S˜ao Paulo 05508-900 SP, Brazil; 2Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista  \nde Medicina, Universidade Federal de S˜ao Paulo, S˜ao Paulo 04023-062 SP, Brazil  \nReceived 8 February 2007; returned 6 April 2007; revised 7 May 2007; accepted 24 May 2007  \nObjectives: This study was performed to investigate the activity of tamoxifen, an antioestrogen widely used in the treatment of breast cancer, against Leishmania.  \nMethods: Drug activity was assessed in vitro against axenically grown promastigotes and amastigotes through cell counting or by measuring the cleavage of MTT, and against intracellular amastigotes by treating infected macrophage cultures and evaluating the number of intracellular parasites.  \nIntravacuolar pH changes induced inside parasitophorous vacuoles of Leishmania (Leishmania) amazonensis-infected macrophages were evaluated using the fluorescent probes SNAFL-calcein and Acridine Orange.  \nResults: Tamoxifen killed L. (L.) amazonensis promastigotes and amastigotes with 50% inhibitory concentrations (IC50) of 16.4 + 0.2 and 11.1 + 0.2 mM, respectively. The drug was also effective against Leishmania (Viannia) braziliensis, Leishmania (Leishmania) major, Leishmania (Leishmania) chagasi and Leishmania (Leishmania) donovani with IC50 values ranging from 9.0 to 20.2 mM. Tamoxifen induced a rapid and long-lasting alkalinization of the vacuolar environment. We also provide evidence that tamoxifen is more effective against promastigotes and amastigotes at pH 7.5 when compared with cultures at pH 4.5.  \nConclusions: Tamoxifen effectively kills several Leishmania species and its activity against the parasite is increased by a modulation of the host cell intravacuolar pH induced by the drug.  \nKeywords: chemotherapy, pH, oestradiol, Acridine Orange, SNAFL-calcein  \nIntroduction  \nHuman leishmaniasis is an endemic disease in 88 countries distributed in tropical and subtropical regions of the world. Clinical manifestations of this parasitic illness vary from self-healing cutaneous ulcers to very aggressive and disfiguring cases of diffuse or mucocutaneous diseases or to the life-threatening visceral form. More than 90% of cutaneous leishmaniasis cases occur in Iran, Afghanistan, Syria, Saudi Arabia, Brazil and Peru.1 In Brazil, Leishmania (Viannia) braziliensis is the most common agent for cutaneous and mucocutaneous leishmaniasis, whereas Leishmania (Leishmania) amazonensis is the most  \nimportant causative agent of the diffuse form of the disease. Chemotherapy of leishmaniasis relies mainly on the administration of pentavalent antimonials that are toxic and poorly tolerated, require daily injections and are becoming ineffective due to the proliferation of resistant parasites.2,3 Therefore, alternative drugs are in pressing need.  \nLeishmania life cycle consists of two distinct forms: promastigotes, flagellated extracellular parasites of the digestive tract of sand flies, and amastigotes, non-flagellated, non-motile stages that live inside parasitophorous vacuoles (PVs) in macrophages of mammalian hosts. The PV encloses a strongly hydrolytic, acid environment—pH around 5.0—and the amastigote does not  \n.............................................................................................................................................................................................................................................................................................................","cbCaihF2pJLH5EVh","https://ap.wps.com/l/cbCaihF2pJLH5EVh","pdf",484726,1,9,"English","en",105,"# Objectives\n## Methods\n## Results\n## Conclusions","[{\"question\":\"What was the study designed to test?\",\"answer\":\"The study investigated the activity of tamoxifen against Leishmania, including multiple species.\"},{\"question\":\"How was tamoxifen activity evaluated in the experiments?\",\"answer\":\"Activity against promastigotes and amastigotes was assessed in vitro by cell counting or by measuring MTT cleavage; intracellular effects were evaluated by treating infected macrophage cultures and counting intracellular parasites.\"},{\"question\":\"What role does intravacuolar pH play in tamoxifen’s effectiveness?\",\"answer\":\"Tamoxifen induces rapid, long-lasting alkalinization of the vacuolar environment, and the activity is higher under conditions such as pH 7.5 compared with more acidic pH (pH 4.5).\"},{\"question\":\"What overall conclusion does the study reach?\",\"answer\":\"Tamoxifen effectively kills several Leishmania species, and its antiparasitic activity is increased by modulation of host-cell intravacuolar pH.\"}]","Antileishmanial activity of tamoxifen - Study objectives, methods, results and conclusions | PDF",1788831337,23,{"code":4,"msg":31,"data":32},"ok",{"site_id":24,"language":23,"slug":33,"title":13,"keywords":34,"description":14,"schema_data":35,"social_meta":91,"head_meta":93,"extra_data":95,"updated_unix":28},"antileishmanial-activity-of-tamoxifen-study-objectives-methods-results-and-conclusions","",{"@graph":36,"@context":90},[37,54,69],{"@type":38,"itemListElement":39},"BreadcrumbList",[40,44,48,51],{"item":41,"name":42,"@type":43,"position":20},"https://docshare.wps.com","Home","ListItem",{"item":45,"name":46,"@type":43,"position":47},"https://docshare.wps.com/document/","Document",2,{"item":49,"name":12,"@type":43,"position":50},"https://docshare.wps.com/document/healthcare/",3,{"item":52,"name":13,"@type":43,"position":53},"https://docshare.wps.com/document/antileishmanial-activity-of-tamoxifen-study-objectives-methods-results-and-conclusions/217177/",4,{"url":52,"name":13,"@type":55,"author":56,"headline":13,"publisher":58,"fileFormat":61,"inLanguage":23,"description":14,"dateModified":62,"datePublished":63,"encodingFormat":61,"isAccessibleForFree":64,"interactionStatistic":65},"DigitalDocument",{"name":9,"@type":57},"Person",{"url":41,"name":59,"@type":60},"DocShare","Organization","application/pdf","2026-09-11","2026-09-08",true,{"@type":66,"interactionType":67,"userInteractionCount":20},"InteractionCounter",{"@type":68},"ViewAction",{"@type":70,"mainEntity":71},"FAQPage",[72,78,82,86],{"name":73,"@type":74,"acceptedAnswer":75},"What was the study designed to test?","Question",{"text":76,"@type":77},"The study investigated the activity of tamoxifen against Leishmania, including multiple species.","Answer",{"name":79,"@type":74,"acceptedAnswer":80},"How was tamoxifen activity evaluated in the experiments?",{"text":81,"@type":77},"Activity against promastigotes and amastigotes was assessed in vitro by cell counting or by measuring MTT cleavage; intracellular effects were evaluated by treating infected macrophage cultures and counting intracellular parasites.",{"name":83,"@type":74,"acceptedAnswer":84},"What role does intravacuolar pH play in tamoxifen’s effectiveness?",{"text":85,"@type":77},"Tamoxifen induces rapid, long-lasting alkalinization of the vacuolar environment, and the activity is higher under conditions such as pH 7.5 compared with more acidic pH (pH 4.5).",{"name":87,"@type":74,"acceptedAnswer":88},"What overall conclusion does the study reach?",{"text":89,"@type":77},"Tamoxifen effectively kills several Leishmania species, and its antiparasitic activity is increased by modulation of host-cell intravacuolar pH.","https://schema.org",{"og:url":52,"og:type":92,"og:title":13,"og:site_name":59,"og:description":14},"article",{"robots":94,"canonical":52},"index,follow",{"doc_id":7,"site_id":24},{"code":4,"msg":5,"data":97},[98,102,106,110,115,120,123,128,132,135,139],{"id":20,"doc_module":4,"doc_module_name":46,"category_name":99,"show_sort_weight":100,"slug":101},"Story & Novel",90,"story-novel",{"id":47,"doc_module":4,"doc_module_name":46,"category_name":103,"show_sort_weight":104,"slug":105},"Literature",80,"literature",{"id":53,"doc_module":4,"doc_module_name":46,"category_name":107,"show_sort_weight":108,"slug":109},"Exam",70,"exam",{"id":111,"doc_module":4,"doc_module_name":46,"category_name":112,"show_sort_weight":113,"slug":114},5,"Comic",60,"comic",{"id":116,"doc_module":4,"doc_module_name":46,"category_name":117,"show_sort_weight":118,"slug":119},6,"Technology",50,"technology",{"id":11,"doc_module":4,"doc_module_name":46,"category_name":12,"show_sort_weight":121,"slug":122},40,"healthcare",{"id":124,"doc_module":4,"doc_module_name":46,"category_name":125,"show_sort_weight":126,"slug":127},8,"Research & Report",30,"research-report",{"id":21,"doc_module":4,"doc_module_name":46,"category_name":129,"show_sort_weight":130,"slug":131},"Religion & Spirituality",20,"religion-spirituality",{"id":130,"doc_module":4,"doc_module_name":46,"category_name":133,"show_sort_weight":130,"slug":134},"World Cup","world-cup",{"id":136,"doc_module":4,"doc_module_name":46,"category_name":137,"show_sort_weight":136,"slug":138},10,"Lifestyle","lifestyle",{"id":140,"doc_module":4,"doc_module_name":46,"category_name":141,"show_sort_weight":111,"slug":142},19,"General","general"]