Skip Navigation



JAC Advance Access published online on April 6, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki090
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
55/5/713    most recent
dki090v2
dki090v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Falk, R.
Right arrow Articles by Polacheck, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Falk, R.
Right arrow Articles by Polacheck, I.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org
Received December 11, 2004
Revised February 1, 2005
Accepted February 7, 2005

Original article

Induction of interleukin-1{beta}, tumour necrosis factor-{alpha} and apoptosis in mouse organs by amphotericin B is neutralized by conjugation with arabinogalactan

Rama Falk 1, Moshe Hacham 1, Abraham Nyska 2, Julie F. Foley 2, Abraham J. Domb 3, and Itzhack Polacheck 1*

1 Department of Clinical Microbiology and Infectious Diseases, The Hebrew University--Hadassah Medical Center, PO Box 12000, Jerusalem 91120, Israel
2 Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC 27709, USA
3 Department of Medicinal Chemistry and Natural Products, The Hebrew University of Jerusalem--School of Pharmacy, PO Box 12065, Jerusalem, Israel

* To whom correspondence should be addressed.
Itzhack Polacheck, E-mail: Itzhack.Polacheck{at}huji.ac.il


  Abstract

Objectives: To investigate the possibilities that: (i) organ toxicity of amphotericin B-deoxycholate (AMB-DOC) is related to induction of interleukin-1{beta} (IL-1{beta}), tumour necrosis factor-{alpha} (TNF-{alpha}) and apoptosis in target organs; and (ii) the reduced toxicity resulting from the conjugation of AMB with water-soluble arabinogalactan (AMB-AG), is related to modulation of these parameters.

Methods: Organ expression of IL-1{beta} and TNF-{alpha} was evaluated by enzyme-linked immunosorbent assay (ELISA) in mouse organ biological fluids and in situ by immunohistochemistry. Tissue damage was evaluated histologically, and apoptosis was demonstrated by terminal dUTP nick end-labelling (TUNEL) staining. AMB-AG conjugate was compared with the micellar (AMB-DOC) and liposomal (AmBisome) AMB formulations.

Results: Treatment with AMB-AG or AmBisome caused no observable histopathological damage in the kidneys. In contrast, treatment with AMB-DOC resulted in disruptive changes and apoptosis in renal tubular cells. These effects were found to correlate with induction of high levels of IL-1{beta} and TNF-{alpha} in kidney lysates. Unlike AMB-AG, AMB-DOC also induced enhanced IL-1{beta} and TNF-{alpha} expression in lysates of lungs, brain, liver and spleen. The marked elevation of these inflammation-apoptosis-promoting cytokines after treatment with AMB-DOC may mediate its systemic and local renal damage. Treatment with AMB-AG (but not AmBisome) appears to uniquely modulate the in situ expression of IL-1{beta} and enhance secretion of TNF-{alpha} in kidneys, effects possibly involved in prevention of apoptosis.

Conclusions: AMB-related toxicity is associated with induction of IL-1{beta}, TNF-{alpha} and apoptosis in organs. These effects were not observed with AMB-AG conjugate, suggesting its potential as a safer formulation for therapy.

Keywords: AMB toxicity; cytokines; AMB formulations; antifungals.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Zhang, H. El-Sikhry, K. R. Chaudhary, S. N. Batchu, A. Shayeganpour, T. O. Jukar, J. A. Bradbury, J. P. Graves, L. M. DeGraff, P. Myers, et al.
Overexpression of CYP2J2 provides protection against doxorubicin-induced cardiotoxicity
Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H37 - H46.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
S. Rama Iniguez, M. A. Dea-Ayuela, J. A. Sanchez-Brunete, J. J. Torrado, J. M. Alunda, and F. Bolas-Fernandez
Real-Time Reverse Transcription-PCR Quantification of Cytokine mRNA Expression in Golden Syrian Hamster Infected with Leishmania infantum and Treated with a New Amphotericin B Formulation.
Antimicrob. Agents Chemother., April 1, 2006; 50(4): 1195 - 1201.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.