PREVENTION OF ADRIAMYCIN AGLYCONE-INDUCED CHANGES OF INNER MITOCHONDRIAL-MEMBRANE PERMEABILITY BY CYCLOSPORINE-A

Authors
Citation
Ia. Alnasser, PREVENTION OF ADRIAMYCIN AGLYCONE-INDUCED CHANGES OF INNER MITOCHONDRIAL-MEMBRANE PERMEABILITY BY CYCLOSPORINE-A, Medical science research, 25(4), 1997, pp. 249-251
Citations number
41
Categorie Soggetti
Medicine, Research & Experimental
Journal title
ISSN journal
02698951
Volume
25
Issue
4
Year of publication
1997
Pages
249 - 251
Database
ISI
SICI code
0269-8951(1997)25:4<249:POAACO>2.0.ZU;2-U
Abstract
The effect of adriamycin aglycone (7-hydroxy aglycone) on the permeabi lity of inner mitochondrial membrane was examined. Tetraphenyl phospho nium ion (TPP+) uptake, estimated with a TPP+-sensitive electrode, was used to monitor changes in isolated heart or liver inner mite chondri al membrane potential. Isolated heart and liver mitochondria were able to accumulate and retain TPP+ after energisation with succinate. Addi tion of adriamycin aglycone (10-150 mu m for heart samples or 50-350 m u m for liver) to the mitochondria led to a loss of the ability of mit ochondria to retain TPP+. The latter is an indication of loss of membr ane potential. Addition of 1 mu m cyclosporin A (CsA) prior to the add ition of succinate abolished the effect of adriamycin aglycone on TPP retention. There is ample evidence that adriamycin-induced cardiotoxi city is related to changes in morphology and/or function of mitochondr ia. The results of this study suggest that adriamycin aglycone induced opening of inner mitochondrial membrane pore which led to the dissipa tion of membrane potential. The effect of adriamycin aglycone was bloc ked by CsA, and thus restored the membrane potential. These results in dicate that CsA may be useful as a protective agent against the toxici ty of adriamycin derivatives.