Carboplatin-induced Fanconi-like syndrome in rats: amelioration by pentoxifylline

Environ Toxicol Pharmacol. 2014 Jan;37(1):185-94. doi: 10.1016/j.etap.2013.11.025. Epub 2013 Dec 6.

Abstract

Introduction: Carboplatin is a congener of cisplatin used in the treatment of ovarian, head and neck and small-cell lung cancer. However, the clinical efficacy of carboplatin is marred by the development of ROS-dependent nephrotoxicity. The pathophysiological damage inflicted upon the kidney by carboplatin closely resembles to that of Fanconi syndrome.

Aims and objectives: The present study aimed at inducing Fanconi-like syndrome in rats by administration of carboplatin. Objectives of the study involved evaluation of biochemical parameters coherent to Fanconi-like syndrome. Further, an attempt was made to evaluate the potential therapeutic effect of pentoxifylline in this condition.

Results: The results of the study demonstrated that the urinary excretion profile of carboplatin treated rats closely resembled to that of patients suffering from Fanconi-like condition. Pentoxifylline was able to ameliorate this nephrotoxic condition as suggested by the change in levels of membrane bound ATPases, MDA and GSH. The urinary levels of tyrosine and cysteine correlate well with that of Fanconi-like condition in animals and humans.

Conclusion: In lieu of these observations, our study suggested that carboplatin-induced renovascular damage resembles to Fanconi-like condition which can be mitigated by pentoxifylline.

Keywords: Carboplatin; Cysteinuria; Fanconi syndrome; Pentoxifylline; Tyrosinuria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Animals
  • Antineoplastic Agents / toxicity*
  • Blood Urea Nitrogen
  • Carboplatin / toxicity*
  • Creatinine / blood
  • Cysteine / urine
  • Female
  • Glutathione / metabolism
  • Hypersensitivity, Delayed / chemically induced*
  • Hypersensitivity, Delayed / drug therapy
  • Hypersensitivity, Delayed / metabolism
  • Immunologic Deficiency Syndromes / chemically induced*
  • Immunologic Deficiency Syndromes / drug therapy
  • Immunologic Deficiency Syndromes / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Pancytopenia / chemically induced*
  • Pancytopenia / drug therapy
  • Pancytopenia / metabolism
  • Pentoxifylline / pharmacology*
  • Pentoxifylline / therapeutic use
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphodiesterase Inhibitors / therapeutic use
  • Rats
  • Rats, Wistar
  • Skin Neoplasms / chemically induced*
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / metabolism
  • Tyrosine / urine
  • Uric Acid / blood

Substances

  • Antineoplastic Agents
  • Phosphodiesterase Inhibitors
  • Uric Acid
  • Tyrosine
  • Malondialdehyde
  • Creatinine
  • Carboplatin
  • Adenosine Triphosphatases
  • Glutathione
  • Cysteine
  • Pentoxifylline

Supplementary concepts

  • Fanconi like syndrome