1. Example of a Bullet Point Slide
Medical faculty
Department of pharmacy
University Novi Sad
Bullet Point 1
Bullet Point 2
Sub Bullet
PROTECTIVE EFFECT OF FULLERENOL C60(OH)24 ON LIPID PEROXIDATION OF RAT TISSUES TREATED WITH DOXORUBICIN
Vukosava Djordjevic Milic1, Branislava Srdjenovic1, Nevena Grujic1, Aleksandar Djordjevic2, Viktorija Dragojevic Simic3, Velibor Vasovic4
1Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Serbia
2 Department of Chemistry, Faculty of Sciences, University of Novi Sad, Serbia
3Centre for Clinical Pharmacology, Military Medical Academy, Belgrade, Serbia
4Department of Pharmacology , Faculty of Medicine, University of Novi Sad, Serbia

2. The anthracycline antibiotic doxorubicin (DOX) is among the most important antitumor agents
14-hydroksy-daunomycin
Doxorubicin is used for more than 30 years in treatment of variety of malignancies.
breast cancer, tumors of bile duct, endometrial tissue, the esophagus and liver, osteosarcomas, soft tissue sarcomas and non-Hodgkin’s lymphoma
adverse effects such as myelosuppression and cardiotoxicity, limits the use of doxorubicin.

3. Number of different mechanisms has been proposed for the cytostatic and cytotoxic activities:
intercalation into DNA with consequent inhibition of macromolecular biosynthesis,
free radical formation with consequent induction of DNA damage or lipid peroxidation,
direct membrane effects and the initiation of DNA damage through inhibition of topoisomerase II in the interaction of these drugs with tumor cell
DNA binding and alkylation,
DNA cross-linking,
Among the mechanisms of doxorubicin toxicity, the most plausible seems to be the increase of free radical production, which induces lipid peroxidation and oxidative damage of cells.

4. Doxorubicin free radical formation
7-deoxyaglycon

5. Lipid peroxidation Alteration of enyzme funiton, Formation of O2•−
modulation of sinthesys of DNA, transcription of RNA
Induction of lipid peroxidation.
Formation of O2•−
Polyunsturated faty acids within phospholipids bilayer of membrane are especially vulnerable to oxidative injury caused by ROS.
end product of lipid peroxidation is malonyldialdehid malondialdehyde (MDA).

6. N-acetil cystein + vitamin E Probucol Deksrazoxan (ICRF -187)
Toxic effects of doxorubicin could be decreased by:
Changing the dosage schedule
Deveoping of new anthracycline antibiotics which are not cardiotoxic
Usage of cytoprotectors
Glutathion
N-acetil cystein + vitamin E
Probucol
Deksrazoxan (ICRF -187)
Amifostin
use of antioxidants as protectors against cell damage by oxidative injury could be potential solution to reduction of toxicity induced by doxorubicin.

7. (Harold W. Kroto, Richard E. Smalley i Robert E. Curl)
fullerenes
Fullerenes are the third allotropic modification of carbon, disocovered in 1985.
(Harold W. Kroto, Richard E. Smalley i Robert E. Curl)

8. fundamental properties of fullerenes such as:
extremely high hydrophobicity
photo activity
high cohesive force between fullerene molecules
ability to accept and release electrons
and relatively high reactivity
allow their structural modification
combinations of nucleophilic and electrophilic additions, cycloadditions and radical additions
it is possible to covalently bond any class of organic compounds to a fullerene core

9. Fullerenol C60(OH)24
Previous investigation discover that in nanomole
concentration and without photoinduction fullerenol
shows :
Radioprotectivity
Antioxidant activity in in vitro systems
Cytotoxicity against some tumor cell lines
It may function as a free radical scavenger and it strongly suppresses cytotoxicity of doxorubicin in the model system.

10. The aim of this study was to investigate the toxic effect of doxorubicin on the rat experimental model and to test usage of a potential protector fullerenol in combination with doxorubicin by measuring product of lipid peroxidation in heart, liver, kidneys, testis and lungs.

11. Chemicals Doksorubicin hydrochloride
Comercial, for i.v. applicaiton - Adrablastina®, Pharmacia & Upjohn, Italy.
Fullerenol C60(OH)24 was synthesized by original method on the Depratment of Chemitrstry, Faculty of sciences, University Novi Sad

12. Experimental animal model
Wistar male rats, wight 180 to 220g, old 8 to 10 weeks
Standard laboratory conditions (room temperature, air humidity, light/dark cycle 12/12, water and food ad libidum I
control group (0.9% saline i.p.) II
doksorubicin (10 mg/ml i.p.)
III
fullerenol 50 mg/kg i.p. 30 minuts before doksorubicin (10 mg/ml i.p.) IV
fullerenol 100 mg/kg i.p. 30 minuts before doksorubicin (10 mg/ml i.p.) V
fullerenol 100 mg/kg i.p
Second and fourteenth day after the treatment, animals were anesthetisized and organs for further analysis were taken.
The samples were homogenized and used for spectrophotometric measurement of the products of lipid peroxidation

13. ___________________________________________________Results______
heart *     
liver      
*p<0.05 related to I; p<0.05 related to II; p<0.05 realted to 2. day

14. ___________________________________________________Results______     
*p<0.05 realted to I;  p<0.05 related to II

15. ___________________________________________________Results______
*p<0.05 realted to I;  p<0.05 related to II

16. Conclusion
Results showed that 2. and 14. days after the treatment, lipid peroxidation was significantly increased only in group treated with doxorubicin
Fullerenol, given as a pretreatment, in both applied dosage, sustained value of the lipid peroxidation of all examined tissues in the level of control
Significantly higher levels of lipid peroxidation, of those obtained in control group, were noticed only in lungs .
Dosage of fullerenol of 100 mg/kg showed better protective effects.
Lipid peroxidation in organs of animals treated only with fullerenol in dosage of 100 mg/kg, was in the control level
These finding imply that fullerenol protect examined organs from oxidative injury caused by doxorubicin, and exhibits antioxidative properties.

17. This work is part of the scientific project funded by Ministry of Science of Republic of Serbia grant No