Potential hepatoprotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas.
The aim of this study was to investigate the potential protective role of fullerenol C60(OH)24 on doxorubicin-induced liver toxicity using in vivo (female Sprague-Dawley rats) and in vitro (human hepatocellular carcinoma - HepG2; colorectal adenocarcinoma cell lines - Caco-2) approaches. The first (healthy control) and second (control with chemically induced mammary carcinomas) group received saline only. The third, fourth and fifth group (all with breast cancer) were injected (i.p.) with a single dose of doxorubicin (8mg/kg), doxorubicin/fullerenol (100mg/kg of fullerenol 30min before administration of 8mg/kg doxorubicin) and fullerenol (100mg/kg), respectively. Two days after treatment, the rats were sacrificed. Results showed that treatment with doxorubicin alone caused significant changes in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), as well as in the levels of malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) in the liver tissue. These effects were significantly reduced for all investigated parameters by pre-treatment with fullerenol but not for the MDA and GSH level. The HepG2 and Caco-2 cell lines were continuously treated with fullerenol for 12h, 24h, 48h and 96h at concentrations of 10microg/mL and 44microg/mL. With the aim of evaluating the modulating activity of fullerenol on doxorubicin-induced hepatotoxicity, the cell lines were simultaneously treated with doxorubicin (1microm; 5microm) and fullerenol (10microg/mL; 44microg/mL) in different combinations. When the cells are treated with 5microm doxorubicin along with the fullerenol, we can see a significant improvement of the cell capability during the entire time-line. We can conclude that fullerenol has cytotoxic effects on HepG2 by itself, but when the oxidative stress is too high the cytotoxic effects of fullerenol are overcome by its protective role as a strong antioxidant compound.
Injac
Rade
R
Faculty of Pharmacy, The Chair of Pharmaceutical Biology, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia. injacrade@gmail.com
Perse
Martina
M
Obermajer
Natasa
N
Djordjevic-Milic
Vukosava
V
Prijatelj
Matevz
M
Djordjevic
Aleksandar
A
Cerar
Anton
A
Strukelj
Borut
B
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D005434:Flow Cytometry; D037741:Fullerenes / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D037741:Fullerenes; D017392:Thiobarbituric Acid Reactive Substances; C108127:fullerenol; D008315:Malondialdehyde; D004317:Doxorubicin; C035749:2-hydroxybutyrate dehydrogenase; D007770:L-Lactate Dehydrogenase; D006884:Hydroxybutyrate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione