Figure 6.

TNF-α enhances the doxorubicin-induced depression of contractile force in human myobundles. Doxorubicin effects on muscle function were measured by assessing twitch and tetanus force. Myobundles were differentiated for 5 days, then doxorubicin was added every 48 hours for 7 days. (A) Myobundle dose response curve of doxorubicin (0.1–1000nM) for tetanic force depression. (B) Representative vehicle and doxorubicin-treated tetanic force traces. C-D: Myobundles were differentiated for 5 days either in the absence [vehicle (0.1% BSA)] or presence of TNF-α (100U/mL), then doxorubicin was added every 48 hours for 7 days either in the presence or absence of 100U/mL TNF-α. The combination of 100U/mL TNF-α and doxorubicin (1–10nM) had a larger effect on twitch force (C) and (D) tetanus force than doxorubicin alone. Data are expressed as mean±SEM of 4 donors with 4 biological replicates.