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Text
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URL Address
<a href="http://doi.org/10.2174/156800912803987968" target="_blank" rel="noreferrer noopener">http://doi.org/10.2174/156800912803987968</a>
Pages
1244–1257
Issue
9
Volume
12
Dublin Core
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Title
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Black currant anthocyanins abrogate oxidative stress through Nrf2- mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma.
Publisher
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Current cancer drug targets
Date
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2012
2012-11
Subject
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Male; Animals; Rats; Diet; Signal Transduction; NF-E2-Related Factor 2/genetics/*metabolism; *Phytotherapy; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Alkylating Agents/toxicity; Anthocyanins/*therapeutic use; Antioxidants/therapeutic use; Diethylnitrosamine/toxicity; Glutathione Transferase; Immunoenzyme Techniques; Lipid Peroxidation/drug effects; Nitric Oxide Synthase Type II/genetics/metabolism; Oxidative Stress/*drug effects; Ribes/*chemistry; Tyrosine/analogs & derivatives/metabolism; Carcinoma; Sprague-Dawley; Blotting; Western; RNA; Liver Neoplasms; Messenger/genetics; Experimental/chemically induced/metabolism/*prevention & control; Hepatocellular/chemically induced/metabolism/*prevention & control
Creator
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Thoppil Roslin J; Bhatia Deepak; Barnes Kendra F; Haznagy-Radnai Erzsebet; Hohmann Judit; Darvesh Altaf S; Bishayee Anupam
Description
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Hepatocellular carcinoma (HCC), considered to be one of the most lethal cancers with almost \textgreater 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.
Identifier
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<a href="http://doi.org/10.2174/156800912803987968" target="_blank" rel="noreferrer noopener">10.2174/156800912803987968</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Phytotherapy
2012
Alkylating Agents/toxicity
Animals
Anthocyanins/*therapeutic use
Antioxidants/therapeutic use
Barnes Kendra F
Bhatia Deepak
Bishayee Anupam
Blotting
Carcinoma
Current cancer drug targets
Darvesh Altaf S
Department of Pharmaceutical Sciences
Diet
Diethylnitrosamine/toxicity
Experimental/chemically induced/metabolism/*prevention & control
Glutathione Transferase
Haznagy-Radnai Erzsebet
Hepatocellular/chemically induced/metabolism/*prevention & control
Hohmann Judit
Immunoenzyme Techniques
Lipid Peroxidation/drug effects
Liver Neoplasms
Male
Messenger/genetics
NEOMED College of Pharmacy
NF-E2-Related Factor 2/genetics/*metabolism
Nitric Oxide Synthase Type II/genetics/metabolism
Oxidative Stress/*drug effects
Rats
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Ribes/*chemistry
RNA
Signal Transduction
Sprague-Dawley
Thoppil Roslin J
Tyrosine/analogs & derivatives/metabolism
Western