Protective effects of caffeic acid phenethyl ester on doxorubicin-induced cardiotoxicity in rats.
The prevention of doxorubicin (DXR)-induced cardiotoxicity may be helpful to improve future DXR therapy. The aim of this study was to investigate the cardio-protective effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, on DXR-induced cardiotoxicity. Rats were divided into three groups and treated with saline, DXR and DXR + CAPE. Rats were treated with CAPE (10 micromol x kg(-1) day(-1) i.p.) or saline starting 2 days before a single dose of DXR (20 mg x kg(-1) i.p.). Ten days later, haemodynamic measurements were performed and the hearts were excised for biochemical analyses and microscopic examination. The heart rate and mean blood pressure were higher and the pulse pressure was lower in the DXR group than in the other two groups. The administration of DXR alone resulted in higher myeloperoxidase activity, lipid peroxidation and protein carbonyl content than in the other groups. The activities of superoxide dismutase and catalase were higher in DXR and DXR + CAPE groups than in the saline group. Rats in the DXR + CAPE group had increased catalase activity in comparison with the DXR group and high glutathione peroxidase activity in comparison with the other two groups. There was severe disruption of mitochondrial fi ne structure in the electron microscopy of the DXR group. In contrast, myocardial microscopy appeared nearly normal in the DXR + CAPE group (as de fi ned at the electron microscopic level). In light of these in vivo haemodynamic, enzymatic and morphological results, we conclude that CAPE pretreatment significantly attenuated DXR-induced cardiac injury, possibly with its antioxidant effects.
Fadillioglu
Ersin
E
Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey. efadillioglu@yahoo.com
Oztas
Emin
E
Erdogan
Hasan
H
Yagmurca
Murat
M
Sogut
Sadik
S
Ucar
Muharrem
M
Irmak
M Kemal
MK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002109:Caffeic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004359:Drug Therapy, Combination; D005979:Glutathione Peroxidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006331:Heart Diseases / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000648:ultrastructure; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002109:Caffeic Acids; D011506:Proteins; D017392:Thiobarbituric Acid Reactive Substances; D004317:Doxorubicin; D002374:Catalase; D009195:Peroxidase; D005979:Glutathione Peroxidase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol