, Volume 38, Issue 2, pp 476–484 | Cite as

Thalidomide Ameliorates Cisplatin-Induced Nephrotoxicity by Inhibiting Renal Inflammation in an Experimental Model

  • Keyvan Amirshahrokhi
  • Ali-Reza Khalili


Cisplatin is a platinum-based chemotherapy drug. However, its chemotherapeutic use is restricted by serious side effects, especially nephrotoxicity. Inflammatory mechanisms have a significant role in the pathogenesis of cisplatin-induced nephrotoxicity. Thalidomide is an immunomodulatory and anti-inflammatory agent and is used for the treatment of various inflammatory diseases. The purpose of this study was to investigate the potential nephroprotective effect of thalidomide in a mouse model of cisplatin-induced nephrotoxicity. Nephrotoxicity was induced in mice by a single injection of cisplatin (15 mg/kg, i.p.) and treated with thalidomide (50 and 100 mg/kg/day, orally) for 4 days, beginning 24 h prior to the cisplatin injection. Renal toxicity induced by cisplatin was demonstrated by increasing plasma levels of creatinine and blood urea nitrogen (BUN). Cisplatin increased the renal production of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β1. In addition, kidney levels of malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) were increased by cisplatin. Biochemical results showed that thalidomide reduced cisplatin-induced increase in plasma creatinine and BUN. Thalidomide treatment also significantly reduced tissue levels of the proinflammatory cytokines, MDA, MPO, and NO and increased anti-inflammatory cytokine IL-10. Furthermore, histological examination indicated that thalidomide ameliorated renal damage caused by cisplatin. These data suggest that thalidomide attenuates cisplatin-induced nephrotoxicity possibly by inhibition of inflammatory reactions. Taken together, our findings indicate that thalidomide might be a valuable candidate for the prevention of nephrotoxicity in patients receiving cisplatin.


cisplatin nephrotoxicity thalidomide cytokines nitric oxide 



This research was supported by a grant from Ardabil University of Medical Sciences.

Conflict of Interest

There are no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Pharmacology, School of PharmacyArdabil University of Medical SciencesArdabilIran
  2. 2.Division of Pathology, Imam HospitalArdabil University of Medical SciencesArdabilIran

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