Black currant anthocyanins abrogate oxidative stress through Nrf2-mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma

Roslin J. Thoppil, Deepak Bhatia, Kendra F. Barnes, Erzsébet Háznagy-Radnai, J. Hohmann, Altaf S. Darvesh, Anupam Bishayee

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC), considered to be one of the most lethal cancers with almost >1 million deaths reported annually worldwide, remains a devastating disease with no known effective cure. Hence, chemopreventive strategies come into play, offering an effective and safe mode of treatment, ideal to ward off potential cancer risks and mortality. A major predisposing condition, pertinent to the development and progression of HCC is oxidative stress. We previously reported a striking chemopreventive effect of anthocyanin-rich black currant skin extract (BCSE) against diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats. The current study aims to elucidate the underlying antioxidant mechanisms of black currant anthocyanins implicated in the previously observed chemopreventive effects against experimental hepatocarcinogenesis. Dietary BCSE (100 and 500 mg/kg) administered four weeks before and 18 weeks after DENA challenge decreased abnormal lipid peroxidation, protein oxidation, and expression of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) in a dose-responsive fashion. Mechanistic studies revealed that BCSE upregulated the gene expression of a number of hepatic antioxidant and carcinogen detoxifying enzymes, such as NAD(P)H:quinone oxidoreductase, glutathione S-transferase, and uridine diphosphate-glucuronosyltransferase isoenzymes, in DENA-initiated animals. Protein and mRNA expressions of nuclear factor E2-related factor 2 (Nrf2) were substantially elevated with BCSE treatment, providing a direct evidence of a coordinated activation of the Nrf2-regulated antioxidant pathway, which led to the upregulation of a variety of housekeeping genes. The results of our study provide substantial evidence that black currant bioactive anthocyanins exert chemopreventive actions against DENA-inflicted hepatocarcinogenesis by attenuating oxidative stress through activation of Nrf2 signaling pathway.

Original languageEnglish
Pages (from-to)1244-1257
Number of pages14
JournalCurrent Cancer Drug Targets
Volume12
Issue number9
Publication statusPublished - 2012

Fingerprint

NF-E2-Related Factor 2
Ribes
Anthocyanins
Diethylnitrosamine
Hepatocellular Carcinoma
Oxidative Stress
Antioxidants
Skin
Glucuronosyltransferase
Uridine Diphosphate
Essential Genes
Nitric Oxide Synthase Type II
Glutathione Transferase
Carcinogens
NAD
Lipid Peroxidation
Isoenzymes
Neoplasms
Oxidoreductases
Proteins

Keywords

  • 3-NT
  • Black currant
  • Chemoprevention
  • Diethylnitrosamine
  • Hepatocarcinogenesis
  • iNOS
  • Nrf2
  • Oxidative stress

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Cancer Research

Cite this

Thoppil, R. J., Bhatia, D., Barnes, K. F., Háznagy-Radnai, E., Hohmann, J., Darvesh, A. S., & Bishayee, A. (2012). Black currant anthocyanins abrogate oxidative stress through Nrf2-mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma. Current Cancer Drug Targets, 12(9), 1244-1257.

Black currant anthocyanins abrogate oxidative stress through Nrf2-mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma. / Thoppil, Roslin J.; Bhatia, Deepak; Barnes, Kendra F.; Háznagy-Radnai, Erzsébet; Hohmann, J.; Darvesh, Altaf S.; Bishayee, Anupam.

In: Current Cancer Drug Targets, Vol. 12, No. 9, 2012, p. 1244-1257.

Research output: Contribution to journalArticle

Thoppil, RJ, Bhatia, D, Barnes, KF, Háznagy-Radnai, E, Hohmann, J, Darvesh, AS & Bishayee, A 2012, 'Black currant anthocyanins abrogate oxidative stress through Nrf2-mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma', Current Cancer Drug Targets, vol. 12, no. 9, pp. 1244-1257.
Thoppil, Roslin J. ; Bhatia, Deepak ; Barnes, Kendra F. ; Háznagy-Radnai, Erzsébet ; Hohmann, J. ; Darvesh, Altaf S. ; Bishayee, Anupam. / Black currant anthocyanins abrogate oxidative stress through Nrf2-mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma. In: Current Cancer Drug Targets. 2012 ; Vol. 12, No. 9. pp. 1244-1257.
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