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


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.


J Hepatol


Journal of hepatology


Di Pascoli M,Diví M,Rodríguez-Vilarrupla A,Rosado E,Gracia-Sancho J,Vilaseca M,Bosch J,García-Pagán JC




Has Abstract


2013-05-01 00:00:00














  • Overexpression of tetraspanin CO-029 in hepatocellular carcinoma.

    abstract:BACKGROUND/AIMS:The molecules involved in the progression of hepatocellular carcinoma (HCC) are not fully understood. The aim of this study was to elucidate the crucial genes involved in cancer progression and metastasis. METHODS:Selectively expressed genes were screened using differential display analysis, and then f...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Kanetaka K,Sakamoto M,Yamamoto Y,Yamasaki S,Lanza F,Kanematsu T,Hirohashi S

    更新日期:2001-11-01 00:00:00

  • Transplantation of the liver in adults and children with fulminant hepatic failure.

    abstract::Fulminant hepatic failure has a high mortality rate despite intensive medical treatment. Urgent hepatic transplantation was considered over a 3 year period in 26 (36%) of 73 patients with the worst prognostic features of fulminant hepatic failure. The criteria for patient selection were based on the duration of advanc...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Vickers C,Neuberger J,Buckels J,McMaster P,Elias E

    更新日期:1988-10-01 00:00:00

  • Portal vein thrombosis, cirrhosis, and liver transplantation.

    abstract::Portal vein thrombosis is not uncommon in candidates for transplantation. Partial thrombosis is more common than complete thrombosis. Despite careful screening at evaluation, a number of patients are still found with previously unrecognized thrombosis per-operatively. The objective is to recanalize the portal vein or,...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Francoz C,Valla D,Durand F

    更新日期:2012-07-01 00:00:00

  • WITHDRAWN: Null genotypes of GSTM1 and GSTT1 both associated with increased hepatocellular carcinoma risk in Asians: new evidence.

    abstract::This article has been withdrawn at the request of the authors and with approval of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Xi B,Zeng T

    更新日期:2011-02-22 00:00:00

  • Management of hepatitis C: current and future perspectives.

    abstract::Chronic hepatitis C is now a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma. In March 1997, the National Institutes of Health sponsored a Consensus Development Conference entitled "Management of Hepatitis C". The final statement from the Consensus Panel set forth clear, evidence-based gui...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Hoofnagle JH

    更新日期:1999-01-01 00:00:00

  • THF gamma 2 stimulates cytokine release by peripheral blood mononuclear cells of patients with chronic hepatitis B virus infection.

    abstract::A recent study indicated that thymic hormones have antiviral effects in human hepatitis B virus infection and woodchuck hepatitis virus infection. These hormones are known to exert immunomodulatory effects on lymphocyte maturation and function; because these are abnormal in patients with chronic hepatitis B virus infe...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Daniels HM,O'Toole A,Hussein MJ,Corridori S,Alexander GJ,Williams R

    更新日期:1994-03-01 00:00:00

  • Demonstration of cooperative contribution of MET- and EGFR-mediated STAT3 phosphorylation to liver regeneration by exogenous suppressor of cytokine signalings.

    abstract:BACKGROUND/AIMS:As conditional knockout mice for stat3 are impaired in liver regeneration after partial hepatectomy while those for gp130 have defects in early STAT3 phosphorylation but have normal DNA synthesis, late STAT3 phosphorylation induced independently of gp130 seems to be essential for liver regeneration. Sin...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Seki E,Kondo Y,Iimuro Y,Naka T,Son G,Kishimoto T,Fujimoto J,Tsutsui H,Nakanishi K

    更新日期:2008-02-01 00:00:00

  • Improved inflammatory activity with peginterferon alfa-2b maintenance therapy in non-cirrhotic prior non-responders: a randomized study.

    abstract:BACKGROUND & AIMS:Therapeutic options for patients failing hepatitis C retreatment are limited. EPIC(3) included a prospective trial assessing long-term peginterferon alfa-2b (PegIFNα-2b) maintenance therapy in patients with METAVIR fibrosis scores (MFS) of F2 or F3 who previously failed hepatitis C retreatment. METHO...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Poynard T,Bruix J,Schiff ER,Diago M,Berg T,Moreno-Otero R,Lyra AC,Carrilho F,Griffel LH,Boparai N,Jiang R,Burroughs M,Brass CA,Albrecht JK

    更新日期:2013-03-01 00:00:00

  • Effect of sensory denervation with capsaicin on liver fibrosis induced by common bile duct ligation in rat.

    abstract::Hepatic fibrosis represents an important stage in the progression of chronic liver disease to cirrhosis. In the present paper we have investigated whether capsaicin-sensitive neuropeptide-containing sensory neurons may participate in the development of liver fibrosis. The expression of hepatic fibrosis induced by comm...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Casini A,Lippe IT,Evangelista S,Geppetti P,Santicioli P,Urso C,Paglierani M,Maggi CA,Surrenti C

    更新日期:1990-11-01 00:00:00

  • Telaprevir with peginterferon and ribavirin for treatment-naive patients chronically infected with HCV of genotype 1 in Japan.

    abstract:BACKGROUND & AIMS:To evaluate the efficacy and safety of telaprevir in combination with peginterferon-α2b (PEG-IFN) and ribavirin (RBV) in patients with chronic hepatitis C. METHODS:In a multi-center randomized clinical trial in Japan, on patients infected with HCV of genotype 1, 126 patients were assigned to telaprev...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Kumada H,Toyota J,Okanoue T,Chayama K,Tsubouchi H,Hayashi N

    更新日期:2012-01-01 00:00:00

  • Alternatively activated macrophages promote resolution of necrosis following acute liver injury.

    abstract:BACKGROUND & AIM:Following acetaminophen (APAP) overdose, acute liver injury (ALI) can occur in patients that present too late for N-acetylcysteine treatment, potentially leading to acute liver failure, systemic inflammation, and death. Macrophages influence the progression and resolution of ALI due to their innate imm...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Starkey Lewis P,Campana L,Aleksieva N,Cartwright JA,Mackinnon A,O'Duibhir E,Kendall T,Vermeren M,Thomson A,Gadd V,Dwyer B,Aird R,Man TY,Rossi AG,Forrester L,Park BK,Forbes SJ

    更新日期:2020-08-01 00:00:00

  • Hedgehog signaling in the liver.

    abstract::Reactivation of Hedgehog (Hh), a morphogenic signaling pathway that controls progenitor cell fate and tissue construction during embryogenesis occurs during many types of liver injury in adult. The net effects of activating the Hedgehog pathway include expansion of liver progenitor populations to promote liver regener...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审


    authors: Omenetti A,Choi S,Michelotti G,Diehl AM

    更新日期:2011-02-01 00:00:00

  • Guinea pig Kupffer cells can be activated in vitro to an enhanced superoxide response. I. Comparison with peritoneal macrophages.

    abstract::Guinea pig Kupffer cells were obtained by partial digestion of the liver with pronase and collagenase and purified by centrifugal elutriation. Cells were kept in monolayer culture and their capacity to secrete superoxide anion in response to phagocytosis of zymosan was determined by the cytochrome c method. Compared t...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Rieder H,Ramadori G,Meyer zum Büschenfelde KH

    更新日期:1988-12-01 00:00:00

  • Inhibition of hepatitis C virus gene expression by adenoviral vectors encoding antisense RNA in vitro and in vivo.

    abstract:BACKGROUND & AIMS:In this study, adenoviral vectors encoding an antisense RNA complementary to the 5' non-coding region (5'NCR) of the HCV-genome were generated to inhibit HCV-RNA gene expression in cell culture and in vivo. METHODS:First and second-generation (with E4-deletion) adenoviruses encoding the HCV5'NCR in a...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: González-Carmona MA,Vogt A,Heinicke T,Quasdorff M,Hoffmann P,Yildiz Y,Schneider C,Serwe M,Bartenschlager R,Sauerbruch T,Caselmann WH

    更新日期:2011-07-01 00:00:00

  • A predictive model of treatment outcome in patients with chronic HCV infection using IL28B and PD-1 genotyping.

    abstract:BACKGROUND & AIMS:The advent of new chronic hepatitis C virus (HCV) therapies requires characterization of patients in order to predict adequate treatment. A good candidate marker is Programmed Cell Death-1 (PD-1) which is involved in progression of HCV infection. The aim of this study was to analyse the effect of seve...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Vidal-Castiñeira JR,López-Vázquez A,Alonso-Arias R,Moro-García MA,Martinez-Camblor P,Melón S,Prieto J,López-Rodriguez R,Sanz-Cameno P,Rodrigo L,Pérez-López R,Pérez-Álvarez R,López-Larrea C

    更新日期:2012-06-01 00:00:00

  • Interferon-gamma produced by interleukin-12-activated tumor infiltrating CD8+T cells directly induces apoptosis of mouse hepatocellular carcinoma.

    abstract:BACKGROUND/AIMS:Interleukin-12 (IL-12), a cytokine with antitumor activity, was examined for the suppressive effect on hepatocellular carcinoma (HCC) in mouse model, and its mechanism of antitumor activity was analyzed. METHODS:Mice implanted with MIH-2 HCC cells were treated with recombinant mouse IL-12 (500 ng/mouse...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Komita H,Homma S,Saotome H,Zeniya M,Ohno T,Toda G

    更新日期:2006-11-01 00:00:00

  • Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study.

    abstract:BACKGROUND/AIMS:Treatment of hepatorenal syndrome (HRS) is based on vasoconstrictors. Terlipressin is the one with the soundest evidence. Noradrenalin has been suggested as an effective alternative. The current study was aimed at assessing the efficacy and safety of noradrenalin vs terlipressin in patients with HRS. M...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,随机对照试验


    authors: Alessandria C,Ottobrelli A,Debernardi-Venon W,Todros L,Cerenzia MT,Martini S,Balzola F,Morgando A,Rizzetto M,Marzano A

    更新日期:2007-10-01 00:00:00

  • Accumulation of proteins bearing atypical isoaspartyl residues in livers of alcohol-fed rats is prevented by betaine administration: effects on protein-L-isoaspartyl methyltransferase activity.

    abstract:BACKGROUND/AIMS:Protein-L-isoaspartyl methyltransferase (PIMT) is a methyltransferase that plays a crucial role in the repair of damaged proteins. In this study, we investigated whether ethanol exposure causes an accumulation of modified proteins bearing atypical isoaspartyl residues that may be related to impaired PIM...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Kharbanda KK,Mailliard ME,Baldwin CR,Sorrell MF,Tuma DJ

    更新日期:2007-06-01 00:00:00

  • Treatment of chronic delta hepatitis with alpha-2 recombinant interferon.

    abstract::The Hepatitis Delta Virus (HDV), a defective ribonucleic acid virus dependent on the Hepatitis B Virus (HBV) is a cause of severe liver disease that often leads to cirrhosis and death. Since the HDV finds in the HBV infection a biological niche in which to thrive indefinitely, the major victims of its infection are th...

    journal_title:Journal of hepatology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Rizzetto M,Rosina F,Saracco G,Bellando PC,Actis GC,Bonino F,Smedile A,Trinchero P,Sansalvadore F,Pintus C

    更新日期:1986-01-01 00:00:00

  • MCD-induced steatohepatitis is associated with hepatic adiponectin resistance and adipogenic transformation of hepatocytes.

    abstract:BACKGROUND/AIMS:In these studies, we tested the hypothesis that increased lipid intake would exacerbate the severity of nutritional steatohepatitis. METHODS:C57Bl/6J mice were fed methionine-and-choline deficient (MCD) diets containing 20% (high) or 5% (low) fat by weight for 3 weeks and compared to lipid-matched cont...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Larter CZ,Yeh MM,Williams J,Bell-Anderson KS,Farrell GC

    更新日期:2008-09-01 00:00:00

  • Pathogenesis of lipid metabolism disorder in hepatitis C: polyunsaturated fatty acids counteract lipid alterations induced by the core protein.

    abstract:BACKGROUND & AIMS:Disturbance in lipid metabolism is one of the features of chronic hepatitis C, being a crucial determinant of the progression of liver fibrosis. Experimental studies have revealed that the core protein of hepatitis C virus (HCV) induces steatosis. METHODS:The activities of fatty acid metabolizing enz...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Miyoshi H,Moriya K,Tsutsumi T,Shinzawa S,Fujie H,Shintani Y,Fujinaga H,Goto K,Todoroki T,Suzuki T,Miyamura T,Matsuura Y,Yotsuyanagi H,Koike K

    更新日期:2011-03-01 00:00:00

  • IL-6 pathway in the liver: From physiopathology to therapy.

    abstract::Interleukin 6 (IL-6) is a pleiotropic four-helix-bundle cytokine that exerts multiple functions in the body. In the liver, IL-6 is an important inducer of the acute phase response and infection defense. IL-6 is furthermore crucial for hepatocyte homeostasis and is a potent hepatocyte mitogen. It is not only implicated...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审


    authors: Schmidt-Arras D,Rose-John S

    更新日期:2016-06-01 00:00:00

  • The non-structural 5A protein of hepatitis C virus exhibits genotypic differences in interferon antagonism.

    abstract:BACKGROUND/AIMS:Patients infected with hepatitis C virus (HCV) genotype 2 or 3 usually respond better to interferon (IFN) treatment than those infected with genotype 1. In this study, we investigated whether the non-structural 5A protein (NS5A) of HCV genotypes 1 and 2 (1b-NS5A and 2a-NS5A, respectively) exerted differ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Tsai YH,Kuang WF,Lu TY,Kao JH,Lai MY,Liu CJ,Chen PJ,Hwang LH

    更新日期:2008-12-01 00:00:00

  • IL-1 receptor like 1 protects against alcoholic liver injury by limiting NF-κB activation in hepatic macrophages.

    abstract:BACKGROUND & AIM:Alcohol consumption increases intestinal permeability and causes damage to hepatocytes, leading to the release of pathogen- and damage-associated molecular pattern molecules (PAMPs and DAMPs), stimulating hepatic macrophages and activating NF-κB. The resultant inflammation exacerbates alcoholic liver d...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Wang M,Shen G,Xu L,Liu X,Brown JM,Feng D,Ross RA,Gao B,Liangpunsakul S,Ju C

    更新日期:2017-09-21 00:00:00

  • Contrast-enhanced ultrasound in the diagnosis of hepatocellular carcinoma.

    abstract::Surveillance of patients at risk of developing hepatocellular carcinoma (HCC) is based on ultrasound (US) examinations performed at either 6 or 12 month intervals. Early detection of HCC in patients with cirrhosis is a challenging issue, since the different entities that are involved in the multi-step process of hepat...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审


    authors: Lencioni R,Piscaglia F,Bolondi L

    更新日期:2008-05-01 00:00:00

  • Transfusion-transmitted hepatitis B virus infection.

    abstract::Hepatitis B virus (HBV) remains a major risk of transfusion-transmitted infection due to the pre-seroconversion window period (WP), infection with immunovariant viruses, and with occult carriage of HBV infection (OBI). Reduction of HBV residual risk depends upon developing more sensitive HBV surface antigen (HBsAg) te...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审


    authors: Candotti D,Allain JP

    更新日期:2009-10-01 00:00:00

  • Inhibition of nitric oxide production increases dimethylnitrosamine-induced liver injury in rats.

    abstract::Intravascular coagulation is involved in the development of certain types of liver injury, including that induced by dimethylnitrosamine. Nitric oxide inhibits platelet aggregation and adhesion; however, its role in protecting against intravascular coagulation has not been clarified. We therefore investigated the effe...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Nagase S,Isobe H,Ayukawa K,Sakai H,Nawata H

    更新日期:1995-11-01 00:00:00

  • Mechanisms of HBV-induced hepatocellular carcinoma.

    abstract::Hepatitis B virus (HBV) contributes to hepatocellular carcinoma (HCC) development through direct and indirect mechanisms. HBV DNA integration into the host genome occurs at early steps of clonal tumor expansion and induces both genomic instability and direct insertional mutagenesis of diverse cancer-related genes. Pro...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审


    authors: Levrero M,Zucman-Rossi J

    更新日期:2016-04-01 00:00:00

  • Natural history of chronic hepatitis B virus-related liver disease and its relationship to serum markers of viral replication.

    abstract::Our understanding of the process whereby replicating Hepatitis B virus is eradicated has been substantially modified by the development of highly sensitive assays of viral replication, such as the detection of HBV-DNA in serum. The implications of these developments on our therapeutic approach in terms of both timing ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Williams R,Alexander GJ

    更新日期:1986-01-01 00:00:00

  • TGF-β-dependent induction of CD4⁺CD25⁺Foxp3⁺ Tregs by liver sinusoidal endothelial cells.

    abstract:BACKGROUND & AIMS:CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) have a profound ability to control immune responses. We have previously shown that the liver is a major source of peripherally induced Tregs. Here, we investigate the liver cell types and molecular mechanisms responsible for hepatic Treg induction. M...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Carambia A,Freund B,Schwinge D,Heine M,Laschtowitz A,Huber S,Wraith DC,Korn T,Schramm C,Lohse AW,Heeren J,Herkel J

    更新日期:2014-09-01 00:00:00