Fullerenol C60(OH)24 prevents doxorubicin-induced acute cardiotoxicity in rats.
Results obtained in vitro suggested that fullerenol's antiproliferative properties and protective effects against doxorubicin (DOX) cytotoxicity are mediated by antioxidative and hydroxyl radical scavenger activity. The aim of this study was to examine the influence of fullerenol on acute cardiotoxicity after the administration of a single high dose of DOX in vivo. The experiment was performed on male Wistar rats randomly divided into five groups, each containing eight individuals, that were treated as follows: I) 0.9% NaCl, II) 10 mg/kg DOX, III) 50 mg/kg fullerenol 30 min before 10 mg/kg DOX, IV) 100 mg/kg fullerenol 30 min before 10 mg/kg DOX, and V) 100 mg/kg fullerenol. A functional, biochemical, hematological, and pathomorphological examination of the heart as well as an evaluation of oxidative stress parameters was conducted on days 2 and 14 after DOX administration. The function of the heart was investigated by monitoring heart contractility after the adrenaline infusion. Fullerenol, applied alone, did not alter basal values of investigated animals. Both doses of fullerenol, used as a pretreatment, did not alter the basal parameters of the animals. The 100 mg/kg dose of fullerenol showed better protection. Considering the mechanisms of DOX toxicity, fullerenol likely exerts its protective role as a free radical sponge and/or by removing free iron through the formation of a fullerenol-iron complex. Our results suggest that fullerenol might be a potential cardioprotective agent in DOX-treated individuals.
Torres
Vukosava Milic
VM
Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, Estação Agronómica Nacional, 2780-157 Oeiras, Portugal. djwukie@gmail.com
Srdjenovic
Branislava
B
Jacevic
Vesna
V
Simic
Viktorija Dragojevic
VD
Djordjevic
Aleksandar
A
Simplício
Ana Luísa
AL
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D004837:Epinephrine / Q000494:pharmacology; D037741:Fullerenes / Q000008:administration & dosage / Q000494:pharmacology*; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D037741:Fullerenes; C408042:fullerol C60(OH)24; D004317:Doxorubicin; D004837:Epinephrine