What is it about?

Doxorubicin (DOX), commonly used antineoplastic agent, affects bone marrow, intestinal tract and heart, but it also has some hepatotoxic effects. Main mechanism of its toxicity is the production of free reactive oxygen species. Polyhidroxilated C60 fullerene derivatives, fullerenol nanoparticles (FNP), act as free radical cavengers in in vitro systems. The aim of the study was to investigate potential FNP protective role against DOX-induced hepatotoxicity in rats. Experiments were performed on adult male Wistar rats. Animals were divided into five groups: (1) 0.9% NaCl (control), (2) 100 mg/kg ip FNP, (3) 10 mg/kg DOX iv, (4) 50 mg/kg ip FNP 30 min before 10mg/kg ivDOX, (5) 100mg/kg ip FNP 30 min before 10mg/kg ivDOX. A general health condition, body and liver weight, TBARS level and antioxidative enzymeactivity, aswell as pathohistological examination of the liver tissue were conducted on days 2 and 14 of the study. FNP, applied alone, did not alter any examinated parameters. However, when used as a pretreatment it significantly increased survival rate, body and liver weight, and decreased TBARS level, antioxidative enzyme activity and hepatic damage score in DOX-treated rats. FNP administered at a dose of 100mg/kg significantly attenuated effects of doxorubicin administered in a single high dose in rats, concerning general condition, body and liver weight, lipid peroxidation level and antioxidative enzyme activity as well as structural alterations of the hepatic tissue.

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Why is it important?

The aim of this study was to examine the effects of fullerenol in the prevention of hepatotoxicity induced by single high dose of DOX in rats. Therefore, measurement of lipid peroxidation, the activity of catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase, aswell as structural examination of the liver have been performed.

Perspectives

Based on these findings it can be concluded that the FNP administered at a dose of 100 mg/kg significantly attenuated effects of DOX administered in a single high dose in rats, concerning general condition, body and liver weight, lipid peroxidation level and antioxidative enzymes activity as well as structural alterations of the hepatic tissue. These results support our hypothesis and previously conducted investigations indicating that FNP possesses high antioxidative and cytoprotective potential. In addition, this study indicates that FNP in dose of 100 mg/kg, not toxic per se, exerts antioxidant effects in vivo, and opens perspectives for its further examination in a variety of other conditions in which increased production of free radicals plays an important role.

Research Professor Vesna Jaćević
National Poison Control Centre, Military Medical Academy & Medical Faculty, University of Defence, Belgrade, Sebia

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This page is a summary of: Fullerenol nanoparticles prevents doxorubicin-induced acute hepatotoxicity in rats, Experimental and Molecular Pathology, April 2017, Elsevier,
DOI: 10.1016/j.yexmp.2017.03.005.
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