Synergistic antifungal activity of statin-azole associations as witnessed by Saccharomyces cerevisiae- and Candida utilis-bioassays and ergosterol quantification.
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| Title: | Synergistic antifungal activity of statin-azole associations as witnessed by Saccharomyces cerevisiae- and Candida utilis-bioassays and ergosterol quantification. |
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| Alternate Title: | Actividad antifúngica sinérgica de combinaciones de estatinas y azólicos revelada mediante bioanálisis con Saccharomyces cerevisiae y Candida utilis y cuantificación de ergosterol. |
| Authors: | Cabral, María Eugenia1, Figueroa, Lucía I. C.1,2, Fariña, Julia I.1 jifarina@proimi.org.ar |
| Source: | Revista Iberoamericana de Micologia. 1/31/2013, Vol. 30 Issue 1, p31-38. 8p. |
| Subjects: | STATINS (Cardiovascular agents), AZOLES, DRUG synergism, SACCHAROMYCES cerevisiae, CANDIDA utilis, BIOLOGICAL assay |
| Abstract (English): | Background: Frequent opportunist fungal infections and the resistance to available antifungal drugs promoted the development of new alternatives for treatment, like antifungal drug combinations. Aims: This work aimed to detect the antifungal synergism between statins and azoles by means of an agar-well diffusion bioassay with 5accharomyces cerevisiae ATCC 32051 and Candida utilis Pr1-2 as test strains. Methods: Synergistic antifungal effects were tested by simultaneously adding a sub inhibitory concentration (SIC) of statin (atorvastatin, lovastatin, pravastatin, rosuvastatin or simvastatin) plus a minimal inhibitory concentration (MIC) of azole (clotrimazole, fluconazole, itraconazole, ketoconazole or miconazole) to yeast-embedded YNB agar plates, and a positive result corresponded to a yeast growth inhibition halo higher than that produced by the MIC of the azole alone. Yeast cell ergosterol quantification by RP-HPLC was used to confirm statin-azole synergism, and ergosterol rescue bioassays were performed for evaluating statin-induced ergosterol synthesis blockage. Results: Growth inhibition was significantly increased when clotrimazole, fluconazole, itraconazole, ketoconazole and miconazole were combined with atorvastatin, lovastatin, rosuvastatin and simvastatin. Highest growth inhibition increments were observed on S. cerevisiae (77.5%) and C utilis (43.2%) with a SIC of simvastatin plus a MIC of miconazole, i.e. 4 + 2.4 µg/ml or 20 + 4.8 µg/ml, respectively. Pravastatin showed almost no significant effects (0-7.6% inhibition increase). Highest interaction ratios between antifungal agents corresponded to simvastatin-miconazole combinations and were indicative of synergism. Synergism was also confirmed by the increased reduction in cellular ergosterol levels (S. cerevisiae, 40% and C utilis, 22%). Statin-induced ergosterol synthesis blockage was corroborated by means of ergosterol rescue bioassays, pravastatin being the most easily abolished inhibition whilst rosuvastatin being the most ergosterol-refractory. Conclusions: Selected statin-azole combinations might be viable alternatives for the therapeutic management of mycosis at lower administration doses or with a higher efficiency. [ABSTRACT FROM AUTHOR] |
| Abstract (Spanish): | Fundamento: La frecuencia de micosis oportunistas y la resistencia a los antimicóticos convencionales han fomentado la búsqueda de nuevas alternativas terapéuticas, como las combinaciones de antimicóticos. Objetivos: El presente estudio trató de detectar el sinergismo antifúngico entre las estatinas y los azólicos mediante un bioanálisis de difusión en pocilios de agar, utilizando Saccharomyces cerevisiae (S. cerevisiae) ATCC 32051 y Candida utilis (C utilis) PR1-2 como cepas de control. Métodos: Los efectos antifúngicos sinérgicos se examinaron mediante la adición simultánea de una concentración sub-inhibitoria (CSI) de estatina (atorvastatina, lovastatina, pravastatina, rosuvas-tatina o simvastatina) más una concentración mínima inhibitoria (CMI) de un azólico (clotrimazol, fluconazol, itraconazol, ketoconazol o miconazol) a placas de agar YNB con las levaduras sembradas por inclusión. Un resultado positivo correspondió a un diámetro del halo de inhibición del crecimiento de la levadura mayor que el producido por la Civil del azólico exclusivo. Para confirmar el sinergismo estatina-azólico, se cuantificó el ergosterol de la membrana celular de las levaduras con cromatografía líquida de alto rendimiento (HPLC-RP). Para valorar la inhibición de la síntesis de ergosterol inducida por estatinas, se emplearon bioanálisis de rescate de ergosterol. Resultados: La inhibición del crecimiento aumentó significativamente cuando se combinaron clotrimazol. fluconazol, itraconazol, ketoconazol y miconazol con atorvastatina, lovastatína, rosuvastatina y simvas-tatina. Los mayores incrementos de la inhibición del crecimiento se observaron en S. cerevisiae (77.5%) y C utilis (43,2%) con una CSI de simvastatina y una CMI de miconazol de 4 + 2,4 µg/ml o 20 + 4,8 µg/ml, respectivamente. Para pravastatina apenas se identificaron efectos significativos (incremento de la inhibición del 0-7,6%). Los mayores cocientes de interacción correspondieron a la combinación de simvastatina y miconazol y fueron indicativos de sinergismo. Este también se confirmó por la mayor disminución de los niveles celulares de ergosterol (S. cerevisiae. 40% y C utilis, 22%). La inhibición de la síntesis de ergosterol inducida por estatinas se corroboró mediante bioanálisis de rescate de ergosterol, donde la inhibición por pravastatina se abolió con facilidad, mientras que la de rosuvastatina fue la más refractaria. Conclusiones: Las combinaciones seleccionadas de estatinas y azólicos podrían ser alternativas viables para el manejo terapéutico de las micosis, en dosis más bajas o con una mayor eficiencia. [ABSTRACT FROM AUTHOR] |
| Copyright of Revista Iberoamericana de Micologia is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | MedicLatina |
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| Items | – Name: Title Label: Title Group: Ti Data: Synergistic antifungal activity of statin-azole associations as witnessed by Saccharomyces cerevisiae- and Candida utilis-bioassays and ergosterol quantification. – Name: TitleAlt Label: Alternate Title Group: TiAlt Data: Actividad antifúngica sinérgica de combinaciones de estatinas y azólicos revelada mediante bioanálisis con Saccharomyces cerevisiae y Candida utilis y cuantificación de ergosterol. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Cabral%2C+María+Eugenia%22">Cabral, María Eugenia</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Figueroa%2C+Lucía+I%2E+C%2E%22">Figueroa, Lucía I. C.</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Fariña%2C+Julia+I%2E%22">Fariña, Julia I.</searchLink><relatesTo>1</relatesTo><i> jifarina@proimi.org.ar</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Revista+Iberoamericana+de+Micologia%22">Revista Iberoamericana de Micologia</searchLink>. 1/31/2013, Vol. 30 Issue 1, p31-38. 8p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22STATINS+%28Cardiovascular+agents%29%22">STATINS (Cardiovascular agents)</searchLink><br /><searchLink fieldCode="DE" term="%22AZOLES%22">AZOLES</searchLink><br /><searchLink fieldCode="DE" term="%22DRUG+synergism%22">DRUG synergism</searchLink><br /><searchLink fieldCode="DE" term="%22SACCHAROMYCES+cerevisiae%22">SACCHAROMYCES cerevisiae</searchLink><br /><searchLink fieldCode="DE" term="%22CANDIDA+utilis%22">CANDIDA utilis</searchLink><br /><searchLink fieldCode="DE" term="%22BIOLOGICAL+assay%22">BIOLOGICAL assay</searchLink> – Name: Abstract Label: Abstract (English) Group: Ab Data: Background: Frequent opportunist fungal infections and the resistance to available antifungal drugs promoted the development of new alternatives for treatment, like antifungal drug combinations. Aims: This work aimed to detect the antifungal synergism between statins and azoles by means of an agar-well diffusion bioassay with 5accharomyces cerevisiae ATCC 32051 and Candida utilis Pr1-2 as test strains. Methods: Synergistic antifungal effects were tested by simultaneously adding a sub inhibitory concentration (SIC) of statin (atorvastatin, lovastatin, pravastatin, rosuvastatin or simvastatin) plus a minimal inhibitory concentration (MIC) of azole (clotrimazole, fluconazole, itraconazole, ketoconazole or miconazole) to yeast-embedded YNB agar plates, and a positive result corresponded to a yeast growth inhibition halo higher than that produced by the MIC of the azole alone. Yeast cell ergosterol quantification by RP-HPLC was used to confirm statin-azole synergism, and ergosterol rescue bioassays were performed for evaluating statin-induced ergosterol synthesis blockage. Results: Growth inhibition was significantly increased when clotrimazole, fluconazole, itraconazole, ketoconazole and miconazole were combined with atorvastatin, lovastatin, rosuvastatin and simvastatin. Highest growth inhibition increments were observed on S. cerevisiae (77.5%) and C utilis (43.2%) with a SIC of simvastatin plus a MIC of miconazole, i.e. 4 + 2.4 µg/ml or 20 + 4.8 µg/ml, respectively. Pravastatin showed almost no significant effects (0-7.6% inhibition increase). Highest interaction ratios between antifungal agents corresponded to simvastatin-miconazole combinations and were indicative of synergism. Synergism was also confirmed by the increased reduction in cellular ergosterol levels (S. cerevisiae, 40% and C utilis, 22%). Statin-induced ergosterol synthesis blockage was corroborated by means of ergosterol rescue bioassays, pravastatin being the most easily abolished inhibition whilst rosuvastatin being the most ergosterol-refractory. Conclusions: Selected statin-azole combinations might be viable alternatives for the therapeutic management of mycosis at lower administration doses or with a higher efficiency. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Abstract (Spanish) Group: Ab Data: Fundamento: La frecuencia de micosis oportunistas y la resistencia a los antimicóticos convencionales han fomentado la búsqueda de nuevas alternativas terapéuticas, como las combinaciones de antimicóticos. Objetivos: El presente estudio trató de detectar el sinergismo antifúngico entre las estatinas y los azólicos mediante un bioanálisis de difusión en pocilios de agar, utilizando Saccharomyces cerevisiae (S. cerevisiae) ATCC 32051 y Candida utilis (C utilis) PR1-2 como cepas de control. Métodos: Los efectos antifúngicos sinérgicos se examinaron mediante la adición simultánea de una concentración sub-inhibitoria (CSI) de estatina (atorvastatina, lovastatina, pravastatina, rosuvas-tatina o simvastatina) más una concentración mínima inhibitoria (CMI) de un azólico (clotrimazol, fluconazol, itraconazol, ketoconazol o miconazol) a placas de agar YNB con las levaduras sembradas por inclusión. Un resultado positivo correspondió a un diámetro del halo de inhibición del crecimiento de la levadura mayor que el producido por la Civil del azólico exclusivo. Para confirmar el sinergismo estatina-azólico, se cuantificó el ergosterol de la membrana celular de las levaduras con cromatografía líquida de alto rendimiento (HPLC-RP). Para valorar la inhibición de la síntesis de ergosterol inducida por estatinas, se emplearon bioanálisis de rescate de ergosterol. Resultados: La inhibición del crecimiento aumentó significativamente cuando se combinaron clotrimazol. fluconazol, itraconazol, ketoconazol y miconazol con atorvastatina, lovastatína, rosuvastatina y simvas-tatina. Los mayores incrementos de la inhibición del crecimiento se observaron en S. cerevisiae (77.5%) y C utilis (43,2%) con una CSI de simvastatina y una CMI de miconazol de 4 + 2,4 µg/ml o 20 + 4,8 µg/ml, respectivamente. Para pravastatina apenas se identificaron efectos significativos (incremento de la inhibición del 0-7,6%). Los mayores cocientes de interacción correspondieron a la combinación de simvastatina y miconazol y fueron indicativos de sinergismo. Este también se confirmó por la mayor disminución de los niveles celulares de ergosterol (S. cerevisiae. 40% y C utilis, 22%). La inhibición de la síntesis de ergosterol inducida por estatinas se corroboró mediante bioanálisis de rescate de ergosterol, donde la inhibición por pravastatina se abolió con facilidad, mientras que la de rosuvastatina fue la más refractaria. Conclusiones: Las combinaciones seleccionadas de estatinas y azólicos podrían ser alternativas viables para el manejo terapéutico de las micosis, en dosis más bajas o con una mayor eficiencia. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Revista Iberoamericana de Micologia is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.riam.2012.09.006 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 8 StartPage: 31 Subjects: – SubjectFull: STATINS (Cardiovascular agents) Type: general – SubjectFull: AZOLES Type: general – SubjectFull: DRUG synergism Type: general – SubjectFull: SACCHAROMYCES cerevisiae Type: general – SubjectFull: CANDIDA utilis Type: general – SubjectFull: BIOLOGICAL assay Type: general Titles: – TitleFull: Synergistic antifungal activity of statin-azole associations as witnessed by Saccharomyces cerevisiae- and Candida utilis-bioassays and ergosterol quantification. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Cabral, María Eugenia – PersonEntity: Name: NameFull: Figueroa, Lucía I. C. – PersonEntity: Name: NameFull: Fariña, Julia I. IsPartOfRelationships: – BibEntity: Dates: – D: 31 M: 01 Text: 1/31/2013 Type: published Y: 2013 Identifiers: – Type: issn-print Value: 11301406 Numbering: – Type: volume Value: 30 – Type: issue Value: 1 Titles: – TitleFull: Revista Iberoamericana de Micologia Type: main |
| ResultId | 1 |
