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

• Carboplatin, like cisplatin, induces ROS-dependent nephrotoxicity.
• Carboplatin induced renal damage resembles Fanconi-like condition.
• Carboplatin intoxication causes aminoaciduria-specifically tyrosinuria and cysteineuria.
• ATPases, GSH and TBARS are affected significantly with carboplatin.
• Pentoxifylline mitigates carboplatin induced renal insult.

IntroductionCarboplatin 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 objectivesThe 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.ResultsThe 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.ConclusionIn lieu of these observations, our study suggested that carboplatin-induced renovascular damage resembles to Fanconi-like condition which can be mitigated by pentoxifylline.

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