Anandamide induces necrosis in primary hepatic stellate cells†‡

Siegmund, Sören; Uchinami, Hiroshi; Osawa, Yosuke; Brenner, David A.; Schwabe, Robert F.

doi:10.1002/hep.20667

Cited by 166 publications

(166 citation statements)

References 50 publications

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“…Nonetheless, the stimulation of CB2 receptor has been shown to have an anti-fibrogenic effect by inducing apoptosis or growth arrest in activated HSCs. 18,19,45 Interestingly, in our study, CB2 receptor expression increased following Rimonabant treatment, whereas that of the CB1 receptor remained unchanged. Although this finding remains unexplained, it is tempting to speculate that by blocking the CB1 receptor, more EC will be available to interact with the CB2 receptor, thus promoting in a positive loop its expression and its antiinflammatory and anti-fibrogenic properties.…”

Section: Endocannabinoids and Liver Cirrhosiscontrasting

confidence: 41%

Reversal of liver fibrosis by the antagonism of endocannabinoid CB1 receptor in a rat model of CCl4-induced advanced cirrhosis

Giannone

Baldassarre

Domenicali

et al. 2012

Laboratory Investigation

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The endocannabinoid system is involved in the pathogenesis of liver fibrosis. Although many substances have been proved to reduce fibrosis in experimental models of chronic liver injury, most of them appear to be effective only if given as a prophylactic or early treatment. This study aimed to explore the effect of pharmacological antagonism of the endocannabinoid cannabinoid type 1 (CB1) receptor started after the stage of full-blown cirrhosis had been reached. Wistar-Han rats with carbon tetrachloride (CCl 4 )-induced cirrhosis were randomized to receive the CB1 receptor antagonist Rimonabant (10 mg/kg/day) or the vehicle for 2 weeks. Age-matched healthy rats served as controls. Liver fibrosis was assessed using Sirius red staining, hydroxyproline concentration and a-smooth muscle actin expression. Hepatic gene expression of mediators of fibrogenesis and inflammation were evaluated by real-time PCR. We also assessed the hepatic expression of CB1 and CB2 receptors and that of the enzymes implicated in the endocannabinoid metabolism. Fibrosis was significantly reduced in rats treated with Rimonabant compared with rats receiving the vehicle. CB1 receptor antagonism limited the gene upregulation of fibrogenic and inflammatory mediators occurring in untreated cirrhotic rats. CB1 and CB2 receptor expression was increased in cirrhotic animals. Interestingly, pharmacological CB1 receptor antagonism was associated with a further induction of the CB2 receptor expression. Regression of fibrosis can be achieved by pharmacological blockade of the CB1 receptor even when started in an advanced stage of the disease. This effect is associated with the suppression of pro-fibrogenic and inflammatory mediators and may have been indirectly favoured by the induction of CB2 receptor expression.

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Section: Endocannabinoids and Liver Cirrhosiscontrasting

confidence: 41%

Reversal of liver fibrosis by the antagonism of endocannabinoid CB1 receptor in a rat model of CCl4-induced advanced cirrhosis

Giannone

Baldassarre

Domenicali

et al. 2012

Laboratory Investigation

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“…51 Anandamide blocks HSC proliferation at concentrations of 1 to 10 micromol/L. At higher concentrations (25-100 micromol/L), anandamide dose-dependently induced cell death in culture-activated and in vivo activated HSCs.…”

Section: B2 Necrosis Of Activated Hscsmentioning

confidence: 92%

Mechanisms of alcohol‐induced hepatic fibrosis

2006

Self Cite

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“…HSCs were isolated from the livers of control mice and of mice 3 weeks after BDL as described previously. 21 The liver was perfused via the inferior vena cava with pronase (EMD Chemicals, Gibbstown, NJ) and collagenase (Roche, Indianapolis, IN). After digestion, the cell suspension was filtered through nylon mesh and purified via 8.2% Nycodenz (AxisShield, Oslo, Norway) gradient centrifugation.…”

Section: Methodsmentioning

confidence: 99%