Evidence that lipid peroxidation by doxorubicin does not initiate the beat inhibition of cultured mouse myocardial cells.

In order to elucidate the biochemical mechanism by which doxorubicin (DX) induces cumulative dose-dependent cardiomyopathy, the effect of DX on beating and on lipid peroxide level in myocardial cells was investigated by using a mouse myocardial cell culture system. Inhibition by DX of the beating of cultured myocardial cells was doseand exposure timedependent. When incubated with DX for 0.5 h, the number of beating cells decreased to 74% at 172 ƒÊm, 52% at 345 ƒÊm and 37% at 517 LM, and the lipid peroxide level in the cells increased significantly at 345 ƒÊm DX or more. At the low dose of 3.5 ƒÊm DX, though the number of beating cells decreased to 72% at 24 h, the lipid peroxide level in the cells was about the same as that without DX at 24 h, and increased to about 1.5 times that of the control at 48 h. Under the same conditions as above, 120ƒÊM ƒ¿tocopherol (Toc) added in advance of the treatment reduced by 86% the lipid peroxidation by DX, but did not protect the beating from DX toxicity. In contrast, 120 ƒÊm coenzyme Q 10 (CoQ 10) reduced the lipid peroxidation by only 33%, but increased the number of beating cells at 48 h from 42% to 68%. We conclude that the lipid peroxidation by DX does not initiate the beat inhibition of cultured myocardial cells, and that the protective effect of CoQ 10 on beating is also based on biochemical actions other than reduction of the lipid peroxidation.