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
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.