Influence of coenzyme Q10 on doxorubicin uptake and metabolism by mouse myocardial cells in culture.

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Abstract
In order to test the hypothesis that coenzyme Q10 (CoQ10) might prevent myocardial cell uptake of doxorubicin (DX), 3H-DX uptake in cultured myocardial cells was studied. When cultured myocardial cells were incubated with 3.5 .mu.M DX for 24-72 h or 140 .mu.M DX for 1-4 h, 120 .mu.M CoQ10 added in advance protected their beating from DX toxicity. However, CoQ10 had no effect on 3H-DX uptake by the cells under the above conditions (3.5 .mu.M DX for 24-72 h or 140 .mu.M DX for 1-4 h). Most of the radioactivity in the cells was recovered as DX itself in both the medium with and without CoQ10. Furthermore, the effects of a CoQ homolog (coenzyme Q9, (CoQ9)) or an analog (plastoquinone (PQ9)) on the beat inhibition by DX were compared using this system. It was shown that CoQ9 prevents, though only partially, the inhibition of the myocardial cell beating by 3.5 .mu.m DX. PQ9 was without effect. It is suggested that the protective effect of CoQ10 against DX cardiotoxicity was not caused by inhibition of DX uptake or by alteration of DX metabolism in the cells.