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Ellagic acid ameliorates cisplatin toxicity in chemically induced colon carcinogenesis

Abstract

Cis-diamminedichloroplatinum(II) (cisplatin) (CP) is an important chemotherapeutic agent used in the treatment of several cancers. However, it has several side effects including nephrotoxicity gonadotoxicity, hepatotoxicity, and ototoxicity. In in vitro experiments, antioxidants or reactive oxygen species scavengers have a cytoprotective effect on cells exposed to cisplatin (CP). Ellagic acid (EA) is one such bioactive polyphenol that is abundant in some fruits, nuts, and seeds. Various authors have reported that EA has strong antioxidant and antitumor potential. The present study was, therefore, carried out to explore the protective potential of EA on CP-induced gonadotoxicity and nephrotoxicity in colon tumor-bearing mice. Animals were divided into five groups: Group I: normal control, Group II: DMH treated. After 20 weeks of DMH treatment, the animals were divided into four subgroups, viz., Group III: no treatment, Group IV: EA, Group V: CP, and Group VI: CP + EA. Administration of EA significantly ameliorated the toxicity caused by CP as indicated by improved kidney function tests and reproductive function tests. EA treatment to CP-abused mice also led to a marked reduction in the extent of peroxidative damage to tissue as was evident from the improvement in the histopathological changes in kidney and testis. Blood counts were also improved on administration of EA to CP-treated mice. This article provides the evidence that antioxidant efficacy of EA has beneficial effects on CP-induced nephrotoxicity and gonadotoxicity and contributes to understanding the role of oxidative stress, and suggests several points as part of the mechanism of CP toxicity.

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Acknowledgements

The present research was supported by the UGC-BSR fellowship in science, New Delhi, India (Award No: F.25-1/2013-14(BSR)/7-209/2009), DST-PURSE Grant, New Delhi, India (Award No: 49/RPC-29/04/16), and the Departmental Grant from the Panjab University, Sector-25, Chandigarh, India.

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Correspondence to Pavitra Ranawat.

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Goyal, Y., Koul, A. & Ranawat, P. Ellagic acid ameliorates cisplatin toxicity in chemically induced colon carcinogenesis. Mol Cell Biochem 453, 205–215 (2019). https://doi.org/10.1007/s11010-018-3446-1

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  • DOI: https://doi.org/10.1007/s11010-018-3446-1

Keywords

  • Cisplatin
  • Colon cancer
  • Nephrotoxicity
  • Testicular-toxicity
  • Ellagic acid