Circulating and hepatic endocannabinoids and endocannabinoid-related molecules in patients with cirrhosis

Caraceni, Paolo; Viola, Antonella; Piscitelli, Fabiana; Giannone, Ferdinando; Berzigotti, Annalisa; Cescon, Matteo; Domenicali, Marco; Petrosino, Stefania; Giampalma, Emanuela; Riili, Anna; Grazi, Gian Luca; Golfieri, Rita; Zoli, Marco; Bernardi, Mauro; Marzo, Vincenzo Di

doi:10.1111/j.1478-3231.2009.02137.x

Cited by 75 publications

(58 citation statements)

References 32 publications

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“…16,39,41 There is a general consensus that the EC system is activated during cirrhosis. 4,5,[44][45][46][47][48] Accordingly, our untreated cirrhotic rats had a significant upregulation of CB1 and CB2 receptors along fibrotic septa and portal tracts where maximal is the presence of activated HSC expressing the CB receptors, as reported by other authors in rats and humans. 4,5,[45][46][47] Furthermore, the downregulation of the enzymes responsible for EC degradation, FAAH and MAGL, represents indirect evidence of increased hepatic EC levels in cirrhotic livers.…”

Section: Endocannabinoids and Liver Cirrhosissupporting

confidence: 86%

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 Cirrhosissupporting

confidence: 86%

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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“…Endocannabinoid levels, such as of 2-AG and AEA are increased in liver disease (14)(15)(16)20). Here, we show that 2-AG and THC induce CB1 mRNA, which is further enhanced by their combination with AA, jointly favoring the progression of fibrosis in ALD.…”

Section: Discussionmentioning

confidence: 50%

“…The significance of ECS in modulating fibrosis, steatosis and cell regeneration in experimental liver injury has been demonstrated and reviewed (7,8,33), and CB receptors are induced in acute and chronic liver injury including cirrhosis (14). However, its involvement in alcoholic liver fibrosis was unknown until the present study, which describes the engagement of ECS in the evolution of alcohol-induced liver fibrosis by showing the expression of CB1 in human ALD, its induction in HSC upon challenge with acetaldehyde and reactive oxygen species and a marked resistance of CB1 -/-mice toward chronic liver injury modulated further by alcohol.…”

Section: Discussionmentioning

confidence: 99%

“…Clinically, patients with chronic hepatitis C and daily canna-bis consumption displayed more severe fibrosis progression than non-or occasional consumers (11)(12)(13). Endocannabinoid expression is faint in patients with healthy livers, whereas in cirrhosis, fatty liver, acute hepatitis or bile duct obstruction, hepatic and serum levels of AEA and 2-AG were found increased (14)(15)(16)(17). Endocannabinoids exert numerous and sometimes opposite effects on liver target cells which could be CB receptor-dependent or independent, and are involved in control of cell survival and apoptosis (18).…”

Section: Introductionmentioning

confidence: 99%

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Cannabinoid Receptor Type I Modulates Alcohol-Induced Liver Fibrosis

Patsenker

Stoll

Millonig

et al. 2011

Mol Med

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“…La cirrosi incrementa l'espressione dei recettori CB 1 nelle cellule endoteliali dei vasi come anche nelle arterie mesenteriche (27,29,30), aumentando in questo modo il grado di vasodilatazione dell'AEA (28,30,32,33,34). Nei pazienti con cirrosi, l'AEA circolante, ma non i livelli di 2-AG, è aumentato nel sangue periferico ma non nelle vene epatiche o nel fegato, suggerendo che il tessuto epatico non è la fonte principale di endocannabinoidi (35).…”

Section: Endocannabimoidi E Alterazioni Emodinamiche Nella Cirrosi Epunclassified

Che cosa so di... Il ruolo della Cannabis e dei Cannabinoidi nelle malattie del fegato: review della letteratura

Vivo¹,

Bellinato²,

Marucco³

et al. 2017

Mission

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IntroduzioneL'utilizzo della cannabis a scopo terapeutico risale a migliaia di anni prima di Cristo, oggi il suo utilizzo è illegale in quasi tutti i paesi occidentali, ma da anni esiste un forte movimento, attivo soprattutto negli Stati Uniti, a favore della sua reintroduzione anche a scopo ricreativo. Ad oggi, sono 20 Stati e il Distretto di Columbia, ad aver approvato regolamenti che hanno permesso di depenalizzare o legalizzare la produzione e l'uso della cannabis a fini terapeutici. Secondo i dati pubblicati dall'International Narcotics Control Board (Narcotic Drugs: Estimated world requirements for 2015; statistics for 2013), i Paesi produttori di cannabis oltre gli Stati Uniti, sono: Canada, Regno Unito, Olanda, Danimarca, Francia, Romania, Repubblica Ceca e Israele.In Italia con il decreto del 9 novembre 2015, il Ministro della Salute ha rilasciato la concessione delle autorizzazioni per la coltivazione, la produzione, la fabbricazione, l'impiego, il commercio, l'esportazione, l'importazione, il transito, l'acquisto, la vendita e la detenzione delle sostanze stupefacenti o psicotrope prestando particolare attenzione ai medicinali di origine vegetale a base di cannabis. La rimborsabilità a carico del Servizio sanitario regionale prevede che la produzione nazionale di sostanze e preparazioni di origine vegetale a base di cannabis, avvenga presso lo Stabilimento chimico farmaceutico militare di Firenze e sia subordinata alle indicazioni emanate da parte delle Regioni o Province autonome. Le regioni che attualmente hanno approvato l'utilizzo della cannabis a scopo terapeutico sono rappresentate da: Puglia, Toscana, Veneto, Liguria, Marche, Friuli Venezia Giulia, Abruzzo, Sicilia, Umbria, Basilicata, Emilia Romagna, Piemonte e Valle D'Aosta. La prescrizione medica di questi preparati non deve essere considerata una terapia propriamente detta, bensì un trattamento sintomatico di supporto ai trattamenti standard, quando questi ultimi non hanno prodotto gli effetti desiderati, hanno provocato effetti secondari non tollerabili, o necessitano di incrementi posologici che potrebbero determinare la comparsa di effetti collaterali . Mission 46.......................................................................................................................................................................................................... SummaryIn many States of USA and some Italian regions, marijuana has been legalized as medical drug. So, a process of cannabis decriminalization is in place throughout the West. The debate about cannabis goes on politically and socially with contrasting aspects. Both as regards the recreational use, it should be recalled that is considered harmful (to a different extent) by virtually all the experts; both in terms of therapeutic use, considered promising by many researchers, but for which the results really sure still seem limited to a few ambit. This paper provides a review to groped to shed light on this topic both on the legal peculiarities and medical prescribing, and espe...

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Circulating and hepatic endocannabinoids and endocannabinoid-related molecules in patients with cirrhosis

Cited by 75 publications

References 32 publications

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

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

Cannabinoid Receptor Type I Modulates Alcohol-Induced Liver Fibrosis

Che cosa so di... Il ruolo della Cannabis e dei Cannabinoidi nelle malattie del fegato: review della letteratura

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