Resveratrol reduces hepatic fibrosis & portal pressure in cirrhotic rats

[StephenCastlecrag]

Journal of Hepatology

Volume 58, Issue 5, May 2013, Pages 904–910

Research Article
Resveratrol improves intrahepatic endothelial dysfunction and reduces hepatic fibrosis and portal pressure in cirrhotic rats

    Marco Di Pascoli†,
    Marta Diví†,
    Aina Rodríguez-Vilarrupla,
    Eugenio Rosado,
    Jorge Gracia-Sancho,
    Marina Vilaseca,
    Jaume Bosch,
    Joan Carles García-PagánCorresponding author contact information, E-mail the corresponding author

    Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Ciberehd, University of Barcelona, Spain

    http://dx.doi.org/10.1016/j.jhep.2012.12.012, How to Cite or Link Using DOI

    
Background & Aims

Resveratrol, a polyphenol found in a variety of fruits, exerts a wide range of beneficial effects on the endothelium, regulates multiple vasoactive substances and decreases oxidative stress, factors involved in the pathophysiology of portal hypertension. Our study aimed at evaluating the effects of resveratrol on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl4 cirrhotic rats.
Methods

Resveratrol (10 and 20 mg/kg/day) or its vehicle was administered to cirrhotic rats for two weeks and hepatic and systemic hemodynamics were measured. Moreover, we evaluated endothelial function by dose-relaxation curves to acetylcholine, hepatic NO bioavailability and TXA2 production. We also evaluated liver fibrosis by Sirius Red staining of liver sections, collagen-1, NFκB, TGFβ mRNA expression, and desmin and α-smooth muscle actin (α-SMA) protein expression, as a surrogate of hepatic stellate cell activation.
Results

Resveratrol administration significantly decreased portal pressure compared to vehicle (12.1 ± 0.9 vs. 14.3 ± 2.2 mmHg; p <0.05) without significant changes in systemic hemodynamics. Reduction in portal pressure was associated with an improved vasodilatory response to acetylcholine, with decreased TXA2 production, increased endothelial NO, and with a significant reduction in liver fibrosis. The decrease in hepatic fibrosis was associated with a reduced collagen-1, TGFβ, NFκB mRNA expression and desmin and α-SMA protein expression.
Conclusions

Resveratrol administration reduces portal pressure, hepatic stellate cell activation and liver fibrosis, and improves hepatic endothelial dysfunction in cirrhotic rats, suggesting it may be a useful dietary supplement in the treatment of portal hypertension in patients with cirrhosis.
Abbreviations

    NO, nitric oxide;
    COX-1, cyclooxygenase-1;
    eNOS, endothelial nitric oxide synthase;
    CCl4, carbon tetrachloride;
    MAP, mmHg, mean arterial pressure;
    PP, mmHg, portal pressure;
    PBF, ml min−1, portal blood flow;
    SMABF, ml min−1, superior mesenteric artery blood flow;
    Mtx, methoxamine;
    Ach, acetylcholine;
    TXB2, thromboxane B2;
    View the MathML sourceO2-, superoxide;
    DHE, dihydroethidium;
    cGMP, cyclic guanosine monophosphate;
    P-eNOS, phosphorylated eNOS;
    α-SMA, α smooth muscle actin

Keywords

    Oxidative stress;
    Endothelial dysfunction;
    Nitric oxide;
    Thromboxane

[ref88]

Joc2011

"Heptech have a Resveratrol brand. Have used it myself. Really good."

Are you referring to the FibroGuard formula? It appears that I can't buy the product direct any more. Any idea?

[stef2011]

i am waiting to see liposomal curcumin, there is a study reporting super anticancer and antinflammatory properties, dont remember if vivo or vitro

this is what they have under development:
• Intra-Cellular Curcumin Cu (ll)
• Intra-Cellular Full Spectrum Omega
• Intra-Cellular CoQ10
• Intra-Cellular Alpha Lipoic Acid with Magnesium
• Intra-Cellular Multi-Vitamin (The world's first)

it would be interesting to ask if they can develop this:
Polyunsaturated liposomes are antiviral against hepatitis B and C

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951407/

[stef2011]

there is also a brand of liposomal reservatrol, in theory this would be the best absolute form for absorption inside cells, but i cannot comment on brand quality because i never order it

Intra-Cellular Resveratrol Liposomal brand MaxHealthLabs.com

[joc2011]

Heptech have a Resveratrol brand. Have used it myself. Really good.

[ref88]

Please refer a reputable brand for Resveratrol for anti-fibrotic benefits? Thanks, VeteranB.

[veteranB]

I can attest to that. Since I added it I feel more energy too.

[April63]

There goes my plan of moving to Southern France.:)
Seriously, thank you for bringing up this valuable point.

[studyforhope]

To get the antifibrotic benefits of Resveratrol you will need much higher doses than what you can get from wine or grapes. 500mg of high purity resveratrol 98% would be my guess for a minimum.

[April63]

Thank you for posting it. It seems like a catch 22. There is resveratrol in the skin of red grapes, in red wine. Yet drinking too much wine will give you cirrhosis.
I guess snacking on red grapes doesn't hurt anyone and could be beneficial.:)

[Dee1956]

This is really interesting, thank you so much for posting.
There used to be a member on here HepatitisResearcher, an MD who said that resveratrol would help us.  Nice to see that it is being documented.
Thank you
Dee