Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part I. Silymarin and its flavonolignans.

Silymarin, an extract of fl avonolignans from the dried fruits of milk thistle (Silybum marianum L. Gaertneri) and its constituents silibinin, dehydrosilibinin, silychristin and silydianin were tested for protective effects on rat cardiomyocytes exposed to doxorubicin. Silymarin and individual fl avonolignans did not exert cytotoxicity in the range 25-100 micro m (incubation 9 h). Dehydrosilibinin was tested only at 25 micro m concentration due to its low solubility. All substances increased the cell ATP level. Silymarin and fl avonolignans displayed a dose-dependent cytoprotection against doxorubicin (100 micro m, incubation 8 h). The protective effects of silymarin, silibinin, dehydrosilibinin and silychristin were comparable to that of dexrasoxane, while silydianin exerted the best protective effect. The ability of silymarin complex and its components to protect cardiomyocytes against doxorubicin-induced oxidative stress is due mainly to their cell membrane stabilization effect, radical scavenging and iron chelating potency. Copyright 2004 John Wiley & Sons, Ltd.