Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes part II.: Caffeic, chlorogenic and rosmarinic acids

The chemoprotective effects of caffeic (CA), chlorogenic (CHA) and rosmarinic (RA) acids were tested against the toxicity of doxorubicin (DOX) in neonatal rat cardiomyocytes and the iron-dependent DOX induced lipid peroxidation of heart membranes, mitochondria and microsomes. The protectivity of these acids was compared with dexrazoxan, used as an adjuvant during DOX chemotherapy. The cytoprotective effects were assessed by enzyme (1,1314 and ASAT) and troponin I leakage, secondly by intracellular ATP content. All hydroxycinnamic acids proved non-cytotoxic, and they stabilized both membranes and the energetic status of cardiomyocytes. After preincubation of cardiomyocytes with the test compounds (100, 200 muM; 1h) the cardiomyocytes were treated with the toxic agent, DOX (100 muM; 8h). The test compounds protected cardiomyocytes against DOX induced oxidative stress (RA > CHA greater than or equal to CA) on all monitored parameters. Substantial preservation of monolayer integrity of the cardiomyocytes by test compounds was also found microscopically. All the acids were more effective in the assays used than dexrazoxan. RA showed the most effective cytoprotectivity. All the acids significantly reduced the iron-dependent DOX induced lipid peroxidation of heart membranes, although of the test compounds, CHA was found to be the most effective (IC50= 8.04 +/- 0.74/6.87 +/- 0.52 muM for microsomes/mitochondria). Copyright (C) 2004 John Wiley Sons, Ltd.