Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated with fullerenol C-60(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 α-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. Copyright © 2008 by Institute of Pharmacology Polish Academy of Sciences.