title: The endocannabinoid system in advanced liver cirrhosis: pathophysiological implication and future perspectives.
abstract: Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules providing different central and peripheral effects that are mediated mostly by the specific receptors CB1 and CB2. The EC system is highly upregulated during chronic liver disease and consistent experimental and clinical findings indicate that it plays a role in the pathogenesis of liver fibrosis and fatty liver disease associated with obesity, alcohol abuse and hepatitis C. Furthermore, a considerable number of studies have shown that EC and their receptors contribute to the pathogenesis of the cardio-circulatory disturbances occurring in advanced cirrhosis, such as portal hypertension, hyperdynamic circulatory syndrome and cirrhotic cardiomyopathy. More recently, the EC system has been implicated in the development of ascites, hepatic encephalopathy and the inflammatory response related to bacterial infection. Rimonabant, a selective CB1 antagonist, was the first drug acting on the EC system approved for the treatment of obesity. Unfortunately, it has been withdrawn from the market because of its neuropsychiatric side effects. Compounds able to target selectively the peripheral CB1 receptors are under evaluation. In addition, molecules stimulating CB2 receptor or modulating the activity of enzymes implicated in EC metabolism are promising areas of pharmacological research. Liver cirrhosis and the related complications represent an important target for the clinical application of these compounds.
authors.affiliation: Department of Medical and Surgical Sciences, Center for Applied Biomedical Research (C.R.B.A.), Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Baldassarre
authors.forename: Ferdinando A
authors.initials: FA
authors.lastname: Giannone
authors.forename: Lucia
authors.initials: L
authors.lastname: Napoli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tovoli
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Ricci
authors.forename: Manuel
authors.initials: M
authors.lastname: Tufoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Caraceni
mesh_terms: D063387:Cannabinoid Receptor Antagonists / Q000627:therapeutic use*; D063388:Endocannabinoids / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008954:Models, Biological; D010880:Piperidines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D000077285:Rimonabant; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D063387:Cannabinoid Receptor Antagonists; D063388:Endocannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D000077285:Rimonabant
keywords: CB1 receptor; CB2 receptor; ascites; cirrhotic cardiomyopathy; endocannabinoids; hyperdynamic circulatory syndrome; liver cirrhosis