Efficacy of netropsin dihydrochloride against the viability, cytopathogenicity and hemolytic activity of Trichomonas vaginalis clinical isolates
Trichomonas vaginalis (T. vaginalis) is a common sexually transmitted infection, affecting the urogenital tract. Trichomoniasis is customarily treated with metronidazole (MTZ). MTZ is known to cause undesirable side effects and there is several reports on MTZ resistant T. vaginalis. Thus, the presen...
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| Veröffentlicht in: | Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2019-12, Vol.25 (12), p.955-964 |
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| container_title | Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy |
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| creator | Abou Gamra, Maha Marzouk Kamel, Hanan Hussein Ezz Eldin, Hayam Mohamed Taha Zahran, Fatima Mohamed |
| description | Trichomonas vaginalis (T. vaginalis) is a common sexually transmitted infection, affecting the urogenital tract. Trichomoniasis is customarily treated with metronidazole (MTZ). MTZ is known to cause undesirable side effects and there is several reports on MTZ resistant T. vaginalis. Thus, the present study aimed to in-vitro evaluate the activity of DNA minor groove binder drug ''Netropsin dihydrochloride'' against metronidazole-sensitive T. vaginalis isolates (G and U isolates) and resistant T. vaginalis isolate (ATCC50138) (R isolate). Netropsin was tested at concentrations ranging from 3.5 to 200 μg/ml. It showed effectiveness against all isolates with MLC of 12.5 μg/ml for G and U isolates and of 25 μg/ml for R isolate. Cytotoxicity assay of isolates exposed to the respective MLC of netropsin for 42 h showed a highly significant reduction in the death percentage of MCDK cell line as compared to the effect elicited by drug free controls. The hemolytic activity was evaluated by hemolytic assay and by monitoring the interaction of T. vaginalis isolates with human erythrocytes by inverted microscopy and scanning electron microscopy. The hemolytic assay showed (0%) hemolysis of RBCs incubated with T. vaginalis isolates treated with the corresponding MLC of netropsin for 24 h. Scanning electron microscopy revealed cytoskeletal deformities of netropsin treated isolates. Taken together, these observations suggest that netropsin is a promising therapy for T. vaginalis infection affecting its viability, virulence, cytopathogenic and hemolytic activity with a mechanism of action that might overcome T. vaginalis resistance to metronidazole. |
| doi_str_mv | 10.1016/j.jiac.2019.05.015 |
| format | Article |
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Trichomoniasis is customarily treated with metronidazole (MTZ). MTZ is known to cause undesirable side effects and there is several reports on MTZ resistant T. vaginalis. Thus, the present study aimed to in-vitro evaluate the activity of DNA minor groove binder drug ''Netropsin dihydrochloride'' against metronidazole-sensitive T. vaginalis isolates (G and U isolates) and resistant T. vaginalis isolate (ATCC50138) (R isolate). Netropsin was tested at concentrations ranging from 3.5 to 200 μg/ml. It showed effectiveness against all isolates with MLC of 12.5 μg/ml for G and U isolates and of 25 μg/ml for R isolate. Cytotoxicity assay of isolates exposed to the respective MLC of netropsin for 42 h showed a highly significant reduction in the death percentage of MCDK cell line as compared to the effect elicited by drug free controls. The hemolytic activity was evaluated by hemolytic assay and by monitoring the interaction of T. vaginalis isolates with human erythrocytes by inverted microscopy and scanning electron microscopy. The hemolytic assay showed (0%) hemolysis of RBCs incubated with T. vaginalis isolates treated with the corresponding MLC of netropsin for 24 h. Scanning electron microscopy revealed cytoskeletal deformities of netropsin treated isolates. Taken together, these observations suggest that netropsin is a promising therapy for T. vaginalis infection affecting its viability, virulence, cytopathogenic and hemolytic activity with a mechanism of action that might overcome T. vaginalis resistance to metronidazole.</description><identifier>ISSN: 1341-321X</identifier><identifier>EISSN: 1437-7780</identifier><identifier>DOI: 10.1016/j.jiac.2019.05.015</identifier><identifier>PMID: 31189504</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Animals ; Anti-Bacterial Agents - pharmacology ; Anti-Bacterial Agents - therapeutic use ; DNA minor groove binder ; Dogs ; Drug Resistance ; Female ; Hemolysis - immunology ; Humans ; Madin Darby Canine Kidney Cells ; MCDK cell line ; Metronidazole - pharmacology ; Metronidazole - therapeutic use ; Metronidazole resistance ; Netropsin ; Netropsin - pharmacology ; Netropsin - therapeutic use ; Parasitic Sensitivity Tests ; Scanning electron microscopy ; T. vaginalis ; Trichomonas vaginalis - drug effects ; Trichomonas vaginalis - immunology ; Trichomonas vaginalis - isolation & purification ; Trichomonas vaginalis - pathogenicity ; Trichomonas Vaginitis - drug therapy ; Trichomonas Vaginitis - parasitology ; Trophozoites - drug effects ; Trophozoites - immunology ; Vagina - parasitology</subject><ispartof>Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 2019-12, Vol.25 (12), p.955-964</ispartof><rights>2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases</rights><rights>Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-8f004a164bff89fef662c2e243536b994632808353111a95d94360dc95b249d63</citedby><cites>FETCH-LOGICAL-c380t-8f004a164bff89fef662c2e243536b994632808353111a95d94360dc95b249d63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27913,27914</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31189504$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abou Gamra, Maha Marzouk</creatorcontrib><creatorcontrib>Kamel, Hanan Hussein</creatorcontrib><creatorcontrib>Ezz Eldin, Hayam Mohamed</creatorcontrib><creatorcontrib>Taha Zahran, Fatima Mohamed</creatorcontrib><title>Efficacy of netropsin dihydrochloride against the viability, cytopathogenicity and hemolytic activity of Trichomonas vaginalis clinical isolates</title><title>Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy</title><addtitle>J Infect Chemother</addtitle><description>Trichomonas vaginalis (T. vaginalis) is a common sexually transmitted infection, affecting the urogenital tract. Trichomoniasis is customarily treated with metronidazole (MTZ). MTZ is known to cause undesirable side effects and there is several reports on MTZ resistant T. vaginalis. Thus, the present study aimed to in-vitro evaluate the activity of DNA minor groove binder drug ''Netropsin dihydrochloride'' against metronidazole-sensitive T. vaginalis isolates (G and U isolates) and resistant T. vaginalis isolate (ATCC50138) (R isolate). Netropsin was tested at concentrations ranging from 3.5 to 200 μg/ml. It showed effectiveness against all isolates with MLC of 12.5 μg/ml for G and U isolates and of 25 μg/ml for R isolate. Cytotoxicity assay of isolates exposed to the respective MLC of netropsin for 42 h showed a highly significant reduction in the death percentage of MCDK cell line as compared to the effect elicited by drug free controls. The hemolytic activity was evaluated by hemolytic assay and by monitoring the interaction of T. vaginalis isolates with human erythrocytes by inverted microscopy and scanning electron microscopy. The hemolytic assay showed (0%) hemolysis of RBCs incubated with T. vaginalis isolates treated with the corresponding MLC of netropsin for 24 h. Scanning electron microscopy revealed cytoskeletal deformities of netropsin treated isolates. Taken together, these observations suggest that netropsin is a promising therapy for T. vaginalis infection affecting its viability, virulence, cytopathogenic and hemolytic activity with a mechanism of action that might overcome T. vaginalis resistance to metronidazole.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>DNA minor groove binder</subject><subject>Dogs</subject><subject>Drug Resistance</subject><subject>Female</subject><subject>Hemolysis - immunology</subject><subject>Humans</subject><subject>Madin Darby Canine Kidney Cells</subject><subject>MCDK cell line</subject><subject>Metronidazole - pharmacology</subject><subject>Metronidazole - therapeutic use</subject><subject>Metronidazole resistance</subject><subject>Netropsin</subject><subject>Netropsin - pharmacology</subject><subject>Netropsin - therapeutic use</subject><subject>Parasitic Sensitivity Tests</subject><subject>Scanning electron microscopy</subject><subject>T. vaginalis</subject><subject>Trichomonas vaginalis - drug effects</subject><subject>Trichomonas vaginalis - immunology</subject><subject>Trichomonas vaginalis - isolation & purification</subject><subject>Trichomonas vaginalis - pathogenicity</subject><subject>Trichomonas Vaginitis - drug therapy</subject><subject>Trichomonas Vaginitis - parasitology</subject><subject>Trophozoites - drug effects</subject><subject>Trophozoites - immunology</subject><subject>Vagina - parasitology</subject><issn>1341-321X</issn><issn>1437-7780</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcuKFDEUhgtRnHH0BVxIli6sMqmkLgE3MowXGHAzgruQSk66TpOqtEm6od7CR540Pbp0dS78_wfn_FX1ltGGUdZ_3Dd71KZpKZMN7RrKumfVNRN8qIdhpM9LzwWrect-XVWvUtpTyoZuHF9WV5yxUXZUXFd_7pxDo81GgiMr5BgOCVdicd5sDGb2IaIFonca15RJnoGcUE_oMW8fiNlyOOg8hx2saMqK6NWSGZbgt4yGaJPxdF4X-ENEM4clrDqRk97hqj0mYjwWp_YEU_A6Q3pdvXDaJ3jzVG-qn1_uHm6_1fc_vn6__XxfGz7SXI-OUqFZLybnRunA9X1rWmgF73g_SSl63o50LBNjTMvOSsF7ao3splZI2_Ob6v2Fe4jh9xFSVgsmA97rFcIxqZYzzjs5CFmk7UVqYkgpglOHiIuOm2JUnZNQe3VOQp2TULRTJYlievfEP04L2H-Wv68vgk8XAZQrTwhRJYOwGrAYwWRlA_6P_wgM450c</recordid><startdate>201912</startdate><enddate>201912</enddate><creator>Abou Gamra, Maha Marzouk</creator><creator>Kamel, Hanan Hussein</creator><creator>Ezz Eldin, Hayam Mohamed</creator><creator>Taha Zahran, Fatima Mohamed</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201912</creationdate><title>Efficacy of netropsin dihydrochloride against the viability, cytopathogenicity and hemolytic activity of Trichomonas vaginalis clinical isolates</title><author>Abou Gamra, Maha Marzouk ; Kamel, Hanan Hussein ; Ezz Eldin, Hayam Mohamed ; Taha Zahran, Fatima Mohamed</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-8f004a164bff89fef662c2e243536b994632808353111a95d94360dc95b249d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>DNA minor groove binder</topic><topic>Dogs</topic><topic>Drug Resistance</topic><topic>Female</topic><topic>Hemolysis - immunology</topic><topic>Humans</topic><topic>Madin Darby Canine Kidney Cells</topic><topic>MCDK cell line</topic><topic>Metronidazole - pharmacology</topic><topic>Metronidazole - therapeutic use</topic><topic>Metronidazole resistance</topic><topic>Netropsin</topic><topic>Netropsin - pharmacology</topic><topic>Netropsin - therapeutic use</topic><topic>Parasitic Sensitivity Tests</topic><topic>Scanning electron microscopy</topic><topic>T. vaginalis</topic><topic>Trichomonas vaginalis - drug effects</topic><topic>Trichomonas vaginalis - immunology</topic><topic>Trichomonas vaginalis - isolation & purification</topic><topic>Trichomonas vaginalis - pathogenicity</topic><topic>Trichomonas Vaginitis - drug therapy</topic><topic>Trichomonas Vaginitis - parasitology</topic><topic>Trophozoites - drug effects</topic><topic>Trophozoites - immunology</topic><topic>Vagina - parasitology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abou Gamra, Maha Marzouk</creatorcontrib><creatorcontrib>Kamel, Hanan Hussein</creatorcontrib><creatorcontrib>Ezz Eldin, Hayam Mohamed</creatorcontrib><creatorcontrib>Taha Zahran, Fatima Mohamed</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abou Gamra, Maha Marzouk</au><au>Kamel, Hanan Hussein</au><au>Ezz Eldin, Hayam Mohamed</au><au>Taha Zahran, Fatima Mohamed</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of netropsin dihydrochloride against the viability, cytopathogenicity and hemolytic activity of Trichomonas vaginalis clinical isolates</atitle><jtitle>Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy</jtitle><addtitle>J Infect Chemother</addtitle><date>2019-12</date><risdate>2019</risdate><volume>25</volume><issue>12</issue><spage>955</spage><epage>964</epage><pages>955-964</pages><issn>1341-321X</issn><eissn>1437-7780</eissn><abstract>Trichomonas vaginalis (T. vaginalis) is a common sexually transmitted infection, affecting the urogenital tract. Trichomoniasis is customarily treated with metronidazole (MTZ). MTZ is known to cause undesirable side effects and there is several reports on MTZ resistant T. vaginalis. Thus, the present study aimed to in-vitro evaluate the activity of DNA minor groove binder drug ''Netropsin dihydrochloride'' against metronidazole-sensitive T. vaginalis isolates (G and U isolates) and resistant T. vaginalis isolate (ATCC50138) (R isolate). Netropsin was tested at concentrations ranging from 3.5 to 200 μg/ml. It showed effectiveness against all isolates with MLC of 12.5 μg/ml for G and U isolates and of 25 μg/ml for R isolate. Cytotoxicity assay of isolates exposed to the respective MLC of netropsin for 42 h showed a highly significant reduction in the death percentage of MCDK cell line as compared to the effect elicited by drug free controls. The hemolytic activity was evaluated by hemolytic assay and by monitoring the interaction of T. vaginalis isolates with human erythrocytes by inverted microscopy and scanning electron microscopy. The hemolytic assay showed (0%) hemolysis of RBCs incubated with T. vaginalis isolates treated with the corresponding MLC of netropsin for 24 h. Scanning electron microscopy revealed cytoskeletal deformities of netropsin treated isolates. Taken together, these observations suggest that netropsin is a promising therapy for T. vaginalis infection affecting its viability, virulence, cytopathogenic and hemolytic activity with a mechanism of action that might overcome T. vaginalis resistance to metronidazole.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>31189504</pmid><doi>10.1016/j.jiac.2019.05.015</doi><tpages>10</tpages></addata></record> |
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| ispartof | Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 2019-12, Vol.25 (12), p.955-964 |
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| subjects | Animals Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents - therapeutic use DNA minor groove binder Dogs Drug Resistance Female Hemolysis - immunology Humans Madin Darby Canine Kidney Cells MCDK cell line Metronidazole - pharmacology Metronidazole - therapeutic use Metronidazole resistance Netropsin Netropsin - pharmacology Netropsin - therapeutic use Parasitic Sensitivity Tests Scanning electron microscopy T. vaginalis Trichomonas vaginalis - drug effects Trichomonas vaginalis - immunology Trichomonas vaginalis - isolation & purification Trichomonas vaginalis - pathogenicity Trichomonas Vaginitis - drug therapy Trichomonas Vaginitis - parasitology Trophozoites - drug effects Trophozoites - immunology Vagina - parasitology |
| title | Efficacy of netropsin dihydrochloride against the viability, cytopathogenicity and hemolytic activity of Trichomonas vaginalis clinical isolates |
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