Fullerenol nanoparticles prevents doxorubicin-induced acute hepatotoxicity in rats.
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 C60fullerene derivatives, fullerenol nanoparticles (FNP), act as free radical scavengers 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) 100mg/kg ip FNP, (3) 10mg/kg DOX iv, (4) 50mg/kg ip FNP 30min before 10mg/kg iv DOX, (5) 100mg/kg ip FNP 30min before 10mg/kg iv DOX. A general health condition, body and liver weight, TBARS level and antioxidative enzyme activity, as well 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.
Department of Experimental Toxicology and Pharmacology, National Poison Control Centre, Military Medical Academy, Belgrade, Serbia; Medical Faculty of the Military Medical Academy, University of Defence, Belgrade, Serbia; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic. Electronic address: vesna.jacevic@vma.mod.gov.rs.
Vesna
V
Jacevic
Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Science, University of Novi Sad, Novi Sad, Serbia.
Aleksandar
A
Djordjevic
Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Branislava
B
Srdjenovic
Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia; Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Lisboa, Portugal.
Vukosava
V
Milic-Tores
Department for Treatment, Military Medical Academy, Belgrade, Serbia; Medical Faculty of the Military Medical Academy, University of Defence, Belgrade, Serbia.
Zoran
Z
Segrt
Centre for Clinical Pharmacology, Military Medical Academy, Belgrade, Serbia; Medical Faculty of the Military Medical Academy, University of Defence, Belgrade, Serbia.
Viktorija
V
Dragojevic-Simic
Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic.
Kamil
K
Kuca
D000208:Acute Disease; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D037741:Fullerenes / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000970:Antineoplastic Agents; D037741:Fullerenes; D017392:Thiobarbituric Acid Reactive Substances; C108127:fullerenol; D004317:Doxorubicin
Doxorubicin; Fullerenol nanoparticles; Hepatic injury; Hepatoprotection; Rats