Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against SystemicCandidaInfection in Mice

Candida albicans causes opportunistic systemic infections with high mortality (30%–50%). Despite significant nephrotoxicity, amphotericin (AmB) is still used for the treatment of this serious fungal infection. Therefore, alternative treatments are urgently needed. Dialyzable leukocyte extracts have...

Descripción completa

Detalles Bibliográficos
Autores principales: Robledo Ávila, F., Pérez Tapia, M., Limón Flores, A., Pavon, L., Hernández Pando, R., Wong Baeza, I., González González, Gloria María, Tovar, C., Estrada Parra, S., Estrada García, I.
Formato: Artículo
Lenguaje:inglés
Publicado: 2013
Materias:
Acceso en línea:http://eprints.uanl.mx/25594/1/25594.pdf
_version_ 1824420253945298944
author Robledo Ávila, F.
Pérez Tapia, M.
Limón Flores, A.
Pavon, L.
Hernández Pando, R.
Wong Baeza, I.
González González, Gloria María
Tovar, C.
Estrada Parra, S.
Estrada García, I.
author_facet Robledo Ávila, F.
Pérez Tapia, M.
Limón Flores, A.
Pavon, L.
Hernández Pando, R.
Wong Baeza, I.
González González, Gloria María
Tovar, C.
Estrada Parra, S.
Estrada García, I.
author_sort Robledo Ávila, F.
collection Repositorio Institucional
description Candida albicans causes opportunistic systemic infections with high mortality (30%–50%). Despite significant nephrotoxicity, amphotericin (AmB) is still used for the treatment of this serious fungal infection. Therefore, alternative treatments are urgently needed. Dialyzable leukocyte extracts have been used successfully to treat patients with mucocutaneous candidiasis, but their effectiveness in systemic candidiasis has not been evaluated. In this study, low-dose AmB (0.1 mg/kg) plus 10 pg of murine dialyzable spleen extracts (mDSE) were tested in a systemic candidiasis mouse model. Survival, tissue fungal burden, kidney damage, kidney cytokines, and serum levels of IL-6 and hepcidin were evaluated. Our results showed that the combined treatment of low-dose AmB plus mDSE improved survival and reduced kidney fungal burden and histopathology; these effects correlated with increased kidney concentration of IFN-γ and TGF-β1, decreased levels of TNF-α, IL-6, and IL-10, as well as high levels of systemic IL-6 and hepcidin. Low-dose AmB and mDSE synergized to clear the infectious agent and reduced tissue damage, confirming the efficacy of a low dose of AmB, which might decrease the risk of drug toxicity. Further studies are necessary to explore these findings and its implications in future therapeutic approaches.
format Article
id eprints-25594
institution UANL
language English
publishDate 2013
record_format eprints
spelling eprints-255942024-03-05T17:58:12Z http://eprints.uanl.mx/25594/ Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against SystemicCandidaInfection in Mice Robledo Ávila, F. Pérez Tapia, M. Limón Flores, A. Pavon, L. Hernández Pando, R. Wong Baeza, I. González González, Gloria María Tovar, C. Estrada Parra, S. Estrada García, I. QR Microbiología Candida albicans causes opportunistic systemic infections with high mortality (30%–50%). Despite significant nephrotoxicity, amphotericin (AmB) is still used for the treatment of this serious fungal infection. Therefore, alternative treatments are urgently needed. Dialyzable leukocyte extracts have been used successfully to treat patients with mucocutaneous candidiasis, but their effectiveness in systemic candidiasis has not been evaluated. In this study, low-dose AmB (0.1 mg/kg) plus 10 pg of murine dialyzable spleen extracts (mDSE) were tested in a systemic candidiasis mouse model. Survival, tissue fungal burden, kidney damage, kidney cytokines, and serum levels of IL-6 and hepcidin were evaluated. Our results showed that the combined treatment of low-dose AmB plus mDSE improved survival and reduced kidney fungal burden and histopathology; these effects correlated with increased kidney concentration of IFN-γ and TGF-β1, decreased levels of TNF-α, IL-6, and IL-10, as well as high levels of systemic IL-6 and hepcidin. Low-dose AmB and mDSE synergized to clear the infectious agent and reduced tissue damage, confirming the efficacy of a low dose of AmB, which might decrease the risk of drug toxicity. Further studies are necessary to explore these findings and its implications in future therapeutic approaches. 2013 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/25594/1/25594.pdf http://eprints.uanl.mx/25594/1.haspreviewThumbnailVersion/25594.pdf Robledo Ávila, F. y Pérez Tapia, M. y Limón Flores, A. y Pavon, L. y Hernández Pando, R. y Wong Baeza, I. y González González, Gloria María y Tovar, C. y Estrada Parra, S. y Estrada García, I. (2013) Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against SystemicCandidaInfection in Mice. Clinical and Developmental Immunology, 2013. pp. 1-7. ISSN 1740-2522 http://doi.org/10.1155/2013/194064 doi:10.1155/2013/194064
spellingShingle QR Microbiología
Robledo Ávila, F.
Pérez Tapia, M.
Limón Flores, A.
Pavon, L.
Hernández Pando, R.
Wong Baeza, I.
González González, Gloria María
Tovar, C.
Estrada Parra, S.
Estrada García, I.
Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against SystemicCandidaInfection in Mice
thumbnail https://rediab.uanl.mx/themes/sandal5/images/online.png
title Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against SystemicCandidaInfection in Mice
title_full Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against SystemicCandidaInfection in Mice
title_fullStr Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against SystemicCandidaInfection in Mice
title_full_unstemmed Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against SystemicCandidaInfection in Mice
title_short Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against SystemicCandidaInfection in Mice
title_sort low dose amphotericin b and murine dialyzable spleen extracts protect against systemiccandidainfection in mice
topic QR Microbiología
url http://eprints.uanl.mx/25594/1/25594.pdf
work_keys_str_mv AT robledoavilaf lowdoseamphotericinbandmurinedialyzablespleenextractsprotectagainstsystemiccandidainfectioninmice
AT pereztapiam lowdoseamphotericinbandmurinedialyzablespleenextractsprotectagainstsystemiccandidainfectioninmice
AT limonfloresa lowdoseamphotericinbandmurinedialyzablespleenextractsprotectagainstsystemiccandidainfectioninmice
AT pavonl lowdoseamphotericinbandmurinedialyzablespleenextractsprotectagainstsystemiccandidainfectioninmice
AT hernandezpandor lowdoseamphotericinbandmurinedialyzablespleenextractsprotectagainstsystemiccandidainfectioninmice
AT wongbaezai lowdoseamphotericinbandmurinedialyzablespleenextractsprotectagainstsystemiccandidainfectioninmice
AT gonzalezgonzalezgloriamaria lowdoseamphotericinbandmurinedialyzablespleenextractsprotectagainstsystemiccandidainfectioninmice
AT tovarc lowdoseamphotericinbandmurinedialyzablespleenextractsprotectagainstsystemiccandidainfectioninmice
AT estradaparras lowdoseamphotericinbandmurinedialyzablespleenextractsprotectagainstsystemiccandidainfectioninmice
AT estradagarciai lowdoseamphotericinbandmurinedialyzablespleenextractsprotectagainstsystemiccandidainfectioninmice