Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated with fullerenol C60(OH)24 via suppression of oxidative stress

Pharmacol Rep. 2008 Sep-Oct;60(5):742-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / antagonists & inhibitors*
  • Antibiotics, Antineoplastic / toxicity*
  • Body Weight / drug effects
  • Catalase / metabolism
  • Doxorubicin / antagonists & inhibitors*
  • Doxorubicin / toxicity*
  • Female
  • Free Radical Scavengers / therapeutic use*
  • Fullerenes / therapeutic use*
  • Glutathione / metabolism
  • Glutathione Reductase / metabolism
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • L-Lactate Dehydrogenase / metabolism
  • Malondialdehyde / metabolism
  • Mammary Neoplasms, Animal / complications*
  • Organ Size / drug effects
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Free Radical Scavengers
  • Fullerenes
  • fullerenol
  • Malondialdehyde
  • Doxorubicin
  • L-Lactate Dehydrogenase
  • Catalase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Glutathione