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

Author:

Djordjević-Milić V.1,Djordjević A.2,Dobrić S.3,Injac Rade4,Vučković D.5,Stankov Karmen6,Dragojević-Simić V.3,Suvajdžić Lj.1

Affiliation:

1. Medical Faculty, Department of Pharmacy

2. Faculty of Science, Department of Chemistry

3. National Poison Control Centre

4. University of Ljubljana

5. Medical Faculty University of Novi Sad

6. Medical Faculty, Department of Biochemistry

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.

Publisher

Trans Tech Publications, Ltd.

Subject

Mechanical Engineering,Mechanics of Materials,Condensed Matter Physics,General Materials Science

Reference11 articles.

1. A.D. Gewitz: Biochemical Pharmacology Vol. 57 (1999), p.727.

2. E.H. Herman and V.J. Ferrans: Pathophysiology of anthracycline cardiotoxicity (New York, Wiley -Liss 1993), pp.25-34.

3. J.H. Doroshow: Cancer Res. Vol. 43 (1983), p.460.

4. E.H. Herman and V.J. Ferrans: Progress in Pediatric Cardiology Vol. 8 (1998), p.49.

5. K. Birandra, et al.: Biochemistry Vol. 26 (1987), p.3776.

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