RGD Reference Report - Black currant phytoconstituents exert chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis by suppression of the inflammatory response. - Rat Genome Database

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Black currant phytoconstituents exert chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis by suppression of the inflammatory response.

Authors: Bishayee, A  Thoppil, RJ  Mandal, A  Darvesh, AS  Ohanyan, V  Meszaros, JG  Haznagy-Radnai, E  Hohmann, J  Bhatia, D 
Citation: Bishayee A, etal., Mol Carcinog. 2011 Dec 27. doi: 10.1002/mc.21860.
RGD ID: 5686872
Pubmed: PMID:22213170   (View Abstract at PubMed)
DOI: DOI:10.1002/mc.21860   (Journal Full-text)

Black currant fruits containing high amounts of anthocyanins are known to possess potent antioxidant and anti-inflammatory properties. We have previously reported that anthocyanin-rich black currant skin extract (BCSE) inhibits diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats although the underlying mechanisms are not fully understood. Our present study investigates the anti-inflammatory mechanisms of BCSE during DENA rat liver carcinogenesis. Dietary BCSE (100 or 500 mg/kg) treatment for 22 wk afforded a striking inhibition of DENA-induced hepatic gamma-glutamyl transpeptidase-positive preneoplastic foci in a dose-responsive fashion. There was a significant increase in hepatic expression of heat shock proteins (HSP70 and HSP90), cyclooxygenase-2, and nuclear factor-kappaB (NF-kappaB) in DENA-exposed rat livers. Dietary BCSE dose-dependently abrogated all these elevated inflammatory markers. The possible cardiotoxicity of BCSE was assessed by monitoring cardiac functions using transthoracic echocardiography. BCSE-mediated anti-inflammatory effects during rat liver carcinogenesis have been achieved without any cardiotoxicity. Our results provide convincing evidence, for the very first time, that suppression of the inflammatory cascade through modulation of the NF-kappaB signaling pathway could be implicated, at least in part, in the chemopreventive effects of black currant bioactive phytoconstituents against experimental hepatocarcinogenesis. These results coupled with an excellent safety profile of BCSE support the development of black currant phytochemicals for the chemoprevention of inflammation-driven hepatocellular cancer. (c) 2011 Wiley Periodicals, Inc.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
liver benign neoplasm  ISOHspa4 (Rattus norvegicus)5686872; 5686872protein:increased expression:liver (rat)RGD 
liver benign neoplasm  IEP 5686872protein:increased expression:liver (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hspa4  (heat shock protein family A (Hsp70) member 4)

Genes (Mus musculus)
Hspa4  (heat shock protein 4)

Genes (Homo sapiens)
HSPA4  (heat shock protein family A (Hsp70) member 4)


Additional Information