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Biological Trace Element Research

, Volume 157, Issue 2, pp 156–163 | Cite as

Comparative In Vivo Evaluations of Curcumin and Its Analog Difluorinated Curcumin Against Cisplatin-Induced Nephrotoxicity

  • Kazim Sahin
  • Cemal Orhan
  • Mehmet Tuzcu
  • Irfana Muqbil
  • Nurhan Sahin
  • Hasan Gencoglu
  • Osman Guler
  • Subhash B. Padhye
  • Fazlul H. Sarkar
  • Ramzi M. Mohammad
Article

Abstract

Curcumin, a polyphenol, has pharmacological effects including antioxidant, anti-inflammatory and anti-cancer features. In this study, we have performed comparative in vivo evaluations of CDF (curcumin difluorinated) and curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) Control; (2) Cisplatin (7 mg/kg body wt, intraperitoneal as a single dose); (3) Cisplatin and CDF (50 mg/rat/day; for 12 days); (4) Cisplatin and curcumin (50 mg/rat/day), for 12 days). Cisplatin treated rats exhibited kidney injury manifested by increased serum N-urea and creatinine (P < 0.001). Kidney from cisplatin treated rats also exhibited significant increase in malondialdehyde (MDA) and 8-isoprostane levels (P < 0.001). Treatment with CDF and curcumin prevented the rise in serum N-urea, creatinine, MDA and 8-isoprostane as compared to experimental control group in kidney (P < 0.05). Compared to curcumin, CDF had greater potential in suppressing cisplatin-induced pro-inflammatory factors NF-κB and COX-2 as well as downstream markers Nrf2 and HO-1 (P < 0.05) in kidney. The analysis on anion transport markers (OAT1 and OAT3) showed a similar trend (CDF > curcumin). CDF could reduce the expression of multi-drug resistance markers OCT1, OCT2, MRP2 and MRP4 to a much greater extent than curcumin (P < 0.05). We also demonstrate that CDF influenced the expression of p-mTOR, p-p70S6K1, p-4E-BP1 and p-Akt. These data suggest that CDF can potentially be used to reduce the chemotherapy induced nephrotoxicity thereby enhancing the therapeutic window of cisplatin. The results also proved that compared to curcumin, CDF has superior protective effect in nephrotoxicity.

Keywords

Curcumin CDF Cisplatin Nephrotoxicity 

Notes

Acknowledgments

The authors thank the Veterinary Control and Research Institute of Elazig for providing the experimental facility and the Turkish Academy of Sciences (TUBA) for providing the fund.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Kazim Sahin
    • 1
  • Cemal Orhan
    • 1
  • Mehmet Tuzcu
    • 2
  • Irfana Muqbil
    • 3
  • Nurhan Sahin
    • 1
  • Hasan Gencoglu
    • 2
  • Osman Guler
    • 4
  • Subhash B. Padhye
    • 5
  • Fazlul H. Sarkar
    • 6
  • Ramzi M. Mohammad
    • 7
  1. 1.Department of Animal Nutrition, Faculty of Veterinary ScienceFirat UniversityElazigTurkey
  2. 2.Department of Biology, Faculty of ScienceFirat UniversityElazigTurkey
  3. 3.Department of Biochemistry, Faculty of Life SciencesAligarh Muslim UniversityAligarhIndia
  4. 4.Department of ToxicologyInstitute of Veterinary ControlElazigTurkey
  5. 5.Department of ChemistryUniversity of PunePuneIndia
  6. 6.Department of Pathology, Wayne State University School of MedicineWayne State UniversityDetroitUSA
  7. 7.Department of Oncology, Karmanos Cancer InstituteWayne State UniversityDetroitUSA

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