Ellagic acid ameliorates cisplatin induced hepatotoxicity in colon carcinogenesis

Environ Toxicol. 2019 Jul;34(7):804-813. doi: 10.1002/tox.22747. Epub 2019 Apr 5.

Abstract

The clinical application of cisplatin (CP), one of the most extensively used antineoplastic drug, is restricted by its numerous side effects. CP's antitumor potential resides in the free generation of reactive oxygen species leading to oxidative stress. This stress is a source of the side effects associated with its use. Ellagic acid (EA), a polyphenol is known to possess multiple health benefits owing to its antioxidant properties. EA is largely metabolized by the colon microbiota of different mammals and therefore was a polyphenol of choice in the present study. The present study was thus carried out to explore the protective potential of EA on CP induced hepatotoxicity in colon tumor bearing mice. The administration of EA (10 mg/kg bwt po daily for 6 weeks) significantly ameliorated the toxicity caused by CP (5 mg/kg bwt ip once a week for 4 weeks). Activities of liver marker enzymes and lactate dehydrogenase were brought back to normal. EA cotreatment also led to a marked reduction in the extent of peroxidative damage to liver tissue as was evident from the improvement in the histopathological changes observed and FT-IR analysis. The present study, therefore, suggests that the administration of EA reduces the CP-induced hepatotoxicity, thereby emerging out as a potential candidate for chemopreventive action.

Keywords: FT-IR; chemotherapy; cisplatin; ellagic acid; hepatotoxicity.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cisplatin / adverse effects*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Cytoprotection / drug effects
  • Ellagic Acid / pharmacology*
  • Liver / drug effects*
  • Liver / physiology
  • Liver Function Tests
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Polyphenols / pharmacology
  • Reactive Oxygen Species / metabolism
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Antioxidants
  • Polyphenols
  • Reactive Oxygen Species
  • Ellagic Acid
  • Cisplatin