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 (LDH 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 microm; 1 h) the cardiomyocytes were treated with the toxic agent, DOX (100 microm; 8 h). The test compounds protected cardiomyocytes against DOX induced oxidative stress (RA > CHA > or = 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 (IC(50) = 8.04 +/- 0.74/6.87 +/- 0.52 micro m for microsomes/mitochondria).
Chlopcíková
Sárka
S
Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Hnevotínská 3, 775 15 Olomouc, Czech Republic.
Psotová
Jitka
J
Miketová
Petra
P
Sousek
Jaromír
J
Lichnovský
Václav
V
Simánek
Vilím
V
D000818:Animals; D002109:Caffeic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002934:Cinnamates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D053630:Depsides; D004317:Doxorubicin; D006331:Heart Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D020128:Inhibitory Concentration 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008861:Microsomes / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010946:Plants, Medicinal; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D000097123:Rosmarinic Acid
D002109:Caffeic Acids; D002726:Chlorogenic Acid; D002934:Cinnamates; D053630:Depsides; D004317:Doxorubicin; D010936:Plant Extracts; D020011:Protective Agents; D000097123:Rosmarinic Acid