Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated with fullerenol C60(OH)24 via suppression of oxidative stress.
Oxidative stress has an important role in the pathogenesis of doxorubicin (DOX)-induced nephrotoxicity. The aim of this study was to investigate the nephroprotective effects of fullerenol (FLR), an antioxidant agent, on DOX-induced nephrotoxicity. The investigation was carried out on adult female Sprague Dawley outbred rats with chemically induced breast cancer (1-methyl-1-nitrosourea; 50 mg/kg; ip). Rats were divided into the following groups: control healthy, control cancer, DOX alone (8 mg/kg, ip, cancer), DOX plus FLR as a pre-treatment (8 mg/kg and 100 mg/kg, respectively, ip, cancer), and FLR alone (100 mg/kg, ip, cancer). At the end of the 2nd day after drug administration, blood and kidney tissues were taken for analysis. The activity of lactate dehydrogenase and alpha-hydroxybutyrate dehydrogenase as serum enzymes, as well as level of malondialdehyde, glutathione, glutathione peroxidase, glutathione reductases, catalase and superoxide dismutase, were determined. DOX caused nephrotoxicity, but FLR pre-treatment prevented oxidative stress, lipid peroxidation and the disbalance of GSH/GSSG levels in kidney tissue caused by DOX. Our results confirm satisfactory nephroprotective efficacy of FLR in the acute phase of toxicity and encourage further studies regarding its use as a potential nephroprotector.
Injac
Rade
R
Faculty of Pharmacy, Institute of Pharmaceutical Biology, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia. injacrade@gmail.com
Boskovic
Marija
M
Perse
Martina
M
Koprivec-Furlan
Eva
E
Cerar
Anton
A
Djordjevic
Aleksandar
A
Strukelj
Borut
B
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D037741:Fullerenes / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000150:complications*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D016166:Free Radical Scavengers; D037741:Fullerenes; C108127:fullerenol; D008315:Malondialdehyde; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione