JAC Advance Access first published online on April 6, 2005
This version published online on April 8, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki090
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Clinical Microbiology and Infectious Diseases, The Hebrew University--Hadassah Medical Center, PO Box 12000, Jerusalem 91120, Israel
* To whom correspondence should be addressed. Objectives:: To investigate the possibilities that: (i) organ toxicity of amphotericin B-deoxycholate (AMB-DOC) is related to induction of interleukin-1 Methods:: Organ expression of IL-1 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 Conclusions:: AMB-related toxicity is associated with induction of IL-1
Received December 11, 2004
Revised February 1, 2005
Accepted February 7, 2005
Original article
Induction of interleukin-1
, tumour necrosis factor-
and apoptosis in mouse organs by amphotericin B is neutralized by conjugation with arabinogalactan
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
Itzhack Polacheck, E-mail: Itzhack.Polacheck{at}huji.ac.il
Abstract 
(IL-1), tumour necrosis factor-
(TNF-) 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. and TNF- 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. and TNF- in kidney lysates. Unlike AMB-AG, AMB-DOC also induced enhanced IL-1 and TNF- 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 and enhance secretion of TNF- in kidneys, effects possibly involved in prevention of apoptosis., TNF- and apoptosis in organs. These effects were not observed with AMB-AG conjugate, suggesting its potential as a safer formulation for therapy.
The originally published version of this article was incorrect. Figure 5 was included twice; once in place of Figure 3. The publisher apologizes for this error.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 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]
|
|