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Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm

BACKGROUND: At present, there is no effective vaccine or other approved product for the prevention of sexually transmitted human immunodeficiency virus type 1 (HIV-1) infection. It has been reported that women in resource-poor communities use vaginally applied citrus juices as topical microbicides....

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Autores principales: Lackman-Smith, Carol S, Snyder, Beth A, Marotte, Katherine M, Osterling, Mark C, Mankowski, Marie K, Jones, Maureen, Nieves-Duran, Lourdes, Richardson-Harman, Nicola, Cummins, James E, Sanders-Beer, Brigitte E
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913913/
https://www.ncbi.nlm.nih.gov/pubmed/20618951
http://dx.doi.org/10.1186/1742-6405-7-22
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author Lackman-Smith, Carol S
Snyder, Beth A
Marotte, Katherine M
Osterling, Mark C
Mankowski, Marie K
Jones, Maureen
Nieves-Duran, Lourdes
Richardson-Harman, Nicola
Cummins, James E
Sanders-Beer, Brigitte E
author_facet Lackman-Smith, Carol S
Snyder, Beth A
Marotte, Katherine M
Osterling, Mark C
Mankowski, Marie K
Jones, Maureen
Nieves-Duran, Lourdes
Richardson-Harman, Nicola
Cummins, James E
Sanders-Beer, Brigitte E
author_sort Lackman-Smith, Carol S
collection PubMed
description BACKGROUND: At present, there is no effective vaccine or other approved product for the prevention of sexually transmitted human immunodeficiency virus type 1 (HIV-1) infection. It has been reported that women in resource-poor communities use vaginally applied citrus juices as topical microbicides. These easily accessible food products have historically been applied to prevent pregnancy and sexually transmitted diseases. The aim of this study was to evaluate the efficacy and cytotoxicity of these substances using an established topical microbicide testing algorithm. Freshly squeezed lemon and lime juice and household vinegar were tested in their original state or in pH neutralized form for efficacy and cytotoxicity in the CCR5-tropic cell-free entry and cell-associated transmission assays, CXCR4-tropic entry and fusion assays, and in a human PBMC-based anti-HIV-1 assay. These products were also tested for their effect on viability of cervico-vaginal cell lines, human cervical explant tissues, and beneficial Lactobacillus species. RESULTS: Natural lime and lemon juice and household vinegar demonstrated anti-HIV-1 activity and cytotoxicity in transformed cell lines. Neutralization of the products reduced both anti-HIV-1 activity and cytotoxicity, resulting in a low therapeutic window for both acidic and neutralized formulations. For the natural juices and vinegar, the IC(50 )was ≤ 3.5 (0.8-3.5)% and the TC(50 )≤ 6.3 (1.0-6.3)%. All three liquid products inhibited viability of beneficial Lactobacillus species associated with vaginal health. Comparison of three different toxicity endpoints in the cervical HeLa cell line revealed that all three products affected membrane integrity, cytosolic enzyme release, and dehydrogenase enzyme activity in living cells. The juices and vinegar also exerted strong cytotoxicity in cervico-vaginal cell lines, mainly due to their acidic pH. In human cervical explant tissues, treatment with 5% lemon or lime juice or 6% vinegar induced toxicity similar to application of 100 μg/ml nonoxynol-9, and exposure to 10% lime juice caused tissue damage comparable to treatment with 5% Triton-X-100. CONCLUSIONS: Lemon and lime juice and household vinegar do not fulfill the safety criteria mandated for a topical microbicide. As a result of their unphysiological formulation for the vaginal tract, they exhibit cytotoxicity to human cell lines, human vaginal tissues, and beneficial vaginal Lactobacillus species.
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spelling pubmed-29139132010-08-03 Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm Lackman-Smith, Carol S Snyder, Beth A Marotte, Katherine M Osterling, Mark C Mankowski, Marie K Jones, Maureen Nieves-Duran, Lourdes Richardson-Harman, Nicola Cummins, James E Sanders-Beer, Brigitte E AIDS Res Ther Research BACKGROUND: At present, there is no effective vaccine or other approved product for the prevention of sexually transmitted human immunodeficiency virus type 1 (HIV-1) infection. It has been reported that women in resource-poor communities use vaginally applied citrus juices as topical microbicides. These easily accessible food products have historically been applied to prevent pregnancy and sexually transmitted diseases. The aim of this study was to evaluate the efficacy and cytotoxicity of these substances using an established topical microbicide testing algorithm. Freshly squeezed lemon and lime juice and household vinegar were tested in their original state or in pH neutralized form for efficacy and cytotoxicity in the CCR5-tropic cell-free entry and cell-associated transmission assays, CXCR4-tropic entry and fusion assays, and in a human PBMC-based anti-HIV-1 assay. These products were also tested for their effect on viability of cervico-vaginal cell lines, human cervical explant tissues, and beneficial Lactobacillus species. RESULTS: Natural lime and lemon juice and household vinegar demonstrated anti-HIV-1 activity and cytotoxicity in transformed cell lines. Neutralization of the products reduced both anti-HIV-1 activity and cytotoxicity, resulting in a low therapeutic window for both acidic and neutralized formulations. For the natural juices and vinegar, the IC(50 )was ≤ 3.5 (0.8-3.5)% and the TC(50 )≤ 6.3 (1.0-6.3)%. All three liquid products inhibited viability of beneficial Lactobacillus species associated with vaginal health. Comparison of three different toxicity endpoints in the cervical HeLa cell line revealed that all three products affected membrane integrity, cytosolic enzyme release, and dehydrogenase enzyme activity in living cells. The juices and vinegar also exerted strong cytotoxicity in cervico-vaginal cell lines, mainly due to their acidic pH. In human cervical explant tissues, treatment with 5% lemon or lime juice or 6% vinegar induced toxicity similar to application of 100 μg/ml nonoxynol-9, and exposure to 10% lime juice caused tissue damage comparable to treatment with 5% Triton-X-100. CONCLUSIONS: Lemon and lime juice and household vinegar do not fulfill the safety criteria mandated for a topical microbicide. As a result of their unphysiological formulation for the vaginal tract, they exhibit cytotoxicity to human cell lines, human vaginal tissues, and beneficial vaginal Lactobacillus species. BioMed Central 2010-07-09 /pmc/articles/PMC2913913/ /pubmed/20618951 http://dx.doi.org/10.1186/1742-6405-7-22 Text en Copyright ©2010 Lackman-Smith et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Lackman-Smith, Carol S
Snyder, Beth A
Marotte, Katherine M
Osterling, Mark C
Mankowski, Marie K
Jones, Maureen
Nieves-Duran, Lourdes
Richardson-Harman, Nicola
Cummins, James E
Sanders-Beer, Brigitte E
Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm
title Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm
title_full Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm
title_fullStr Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm
title_full_unstemmed Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm
title_short Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm
title_sort safety and anti-hiv assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913913/
https://www.ncbi.nlm.nih.gov/pubmed/20618951
http://dx.doi.org/10.1186/1742-6405-7-22
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