title: Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated with fullerenol C60(OH)24 via suppression of oxidative stress.
abstract: 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.
authors.affiliation: Faculty of Pharmacy, Institute of Pharmaceutical Biology, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia. injacrade@gmail.com
authors.forename: Rade
authors.initials: R
authors.lastname: Injac
authors.forename: Marija
authors.initials: M
authors.lastname: Boskovic
authors.forename: Martina
authors.initials: M
authors.lastname: Perse
authors.forename: Eva
authors.initials: E
authors.lastname: Koprivec-Furlan
authors.forename: Anton
authors.initials: A
authors.lastname: Cerar
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Djordjevic
authors.forename: Borut
authors.initials: B
authors.lastname: Strukelj
mesh_terms: 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
chemical_list: 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