Influence of Fullerenol C₆₀(OH)₂₄ on Doxorubicin Induced Cardiotoxicity in Rats

Abstract

Earlier investigation of fullerenol, C60(OH)24, features, in vitro, showed that fullerenol have strong antioxidative potential. In this work, we examined the influence of fullerenol as a potential antioxidative protector on doxorubicin induced cardiotoxicity in rats. Experiments were performed on adult Wistar rats, both gender. Animals were divided into six groups, each containing eight individuals. Doxorubicin was administrated i.v. (tail vein) in single dose of 8mg/kg. Fullerenol C60(OH)24 in treated animals was administrated i.p. (in doses 50, 100, 200 mg/kg) for 30 min. before application of doxorubicin. Control group (intact animals) was given saline (1 mL/kg). One group was treated only with fullerenol (100 mg/kg i.p.). Cardiotoxicity of doxorubicin as well as cardioprotective effects of fullerenol were evaluated following the heart function monitored by ECG recording during adrenalin i.v. infusion, and pathomorphological examination of the heart tissue. These evaluations were performed on the day 2 and 7 after doxorubicin administration. Both functional and pathomorphological investigations revealed no heart damage two days after given treatments. However, on the day 7 after doxorubicin injection, changes in cardiovascular reflexes to adrenalin as well as structural damage were manifest. The time for appearance of adrenalin-induced reflex bradicardia in ECG record was significantly longer in doxorubicin treated group in comparison with the control one. Also, pathomorphological examination of the heart tissue showed vacuolization of cardiomyocites. In fullerenol pretreated groups these described changes were ameliorated and corresponded to the control values. These results suggest that fullerenol might be potential cardioprotector in doxorubicin treated individuals.

Biological applications of hydrophilic C60 derivatives (hC60s)− a structural perspective

“…The DOX alone group led to adrenalin-induced reflex bradycardia and vacuolization of cardiomyocites. The pre-treated C60(OH)24 group delayed or even diminished these side effects [29]. In addition, 100 mg/kg C60(OH)24 maintained the level of antioxidative enzymes superoxide in cardiomyocytes which would be enhanced by 8 mg/kg DOX.…”

“…C60(OH)24 was obtained by the derivatization of C60Br24, which was afforded by C60 and bromide in the presence of catalytic amount of FeBr3 with the yield of 98% [29,34]. The above toxicities were attributed to free radicals generated by DOX in vivo.…”

“…C60(OH)24 is taken as an antioxidant protector against the cardiotoxicity, pulmotoxicity, nephrotoxicity and hepatotoxicity induced by DOX [29][30][31][32][33]. C60(OH)24 was obtained by the derivatization of C60Br24, which was afforded by C60 and bromide in the presence of catalytic amount of FeBr3 with the yield of 98% [29,34].…”

“…Fullerenol and C60(C(COOH)2)3 with large aggregation erase radicals [29][30][31][32][33]144]. Their main ability is radical scavenging.…”

Bioimpact of Carbon Nanomaterials

“…According to preliminary studies on healthy adult Wistar rats [75,72], it was established that 100 mg/kg (i.p.) of fullerenol administered 30 min before doxorubicin has a potential protective infl uence on heart and liver tissue.…”