Rhein enhances the effect of adriamycin on mitochondrial respiration by increasing antibiotic-membrane interaction.
The effect of the combination of Adriamycin (ADM) with rhein (RH), an anti-inflammatory drug, on the electron flow through site III and IV of the respiratory chain of rat liver mitochondria was investigated. RH, even at high concentrations, does not inhibit either duroquinol (DHQ) oxidation or cytochrome oxidase activity both of which are decreased by ADM in a dose-dependent manner. The analysis of interaction, performed with the isobolar method, shows a strong synergistic effect that cannot be ascribed to increased permeability of the mitochondrial membranes brought about by RH. The mechanism by which RH potentiates the effect of ADM on DHQ oxidation and cytochrome oxidase activity is most likely to be changes induced in the physical status of the inner mitochondrial membrane such as to permit low ADM concentrations to bind and segregate enough cardiolipin to inhibit electron transport through complex III and IV.
Floridi
A
A
Laboratory of Cell Metabolism and Pharmacokinetics, Regina Elena Institute for Cancer Research, Rome, Italy.
Pulselli
R
R
Gentile
F P
FP
Barbieri
R
R
Benassi
M
M
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D003576:Electron Transport Complex IV / Q000378:metabolism; D006873:Hydroquinones / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley
D000880:Anthraquinones; D006873:Hydroquinones; D004317:Doxorubicin; D003576:Electron Transport Complex IV; C016421:duroquinol; C020491:rhein