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

Silymarin, an extract of flavonolignans 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 flavonolignans did not exert cytotoxicity in the range 25-100 mum (incubation 9 h). Dehydrosilibinin was tested only at 25 mum concentration due to its low solubility. All substances increased the cell ATP level. Silymarin and flavonolignans displayed a dose-dependent cytoprotection against doxorubicin (100 mum, 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 (C) 2004 John Wiley Sons, Ltd.