The endocannabinoid system as a novel target for the treatment of liver fibrosis

[Jarod]

http://www.ncbi.nlm.nih.gov/pubmed/17412522

The endocannabinoid system as a novel target for the treatment of liver fibrosis
[Article in French]
Teixeira-Clerc F, Julien B, Grenard P, Tran Van Nhieu J, Deveaux V, Hezode C, Mallat A, Lotersztajn S.
Source

Inserm, unité 841, IMRB, 94000 Créteil, France.
Abstract

The cannabinoid system comprises specific G protein-coupled receptors (CB1 and CB2), exogenous (marijuana-derived cannabinoids) and endogenous (endocannabinoids) ligands, and a machinery dedicated to endocannabinoid synthesis and degradation. Studies over two decades have extensively documented the crucial role of the cannabinoid system in the regulation of a variety of pathophysiological conditions. However, its role in liver pathology has only been recently unravelled, probably given the low expression of CB1 and CB2 in the normal liver. We have recently demonstrated that CB1 and CB2 receptors display opposite effects in the regulation of liver fibrogenesis during chronic liver injury. Indeed, both receptors are up-regulated in the liver of cirrhotic patients, and expressed in liver fibrogenic cells. Moreover, CB1 receptors are profibrogenic and accordingly, the CB1 antagonist rimonabant reduces fibrosis progression in three experimental models. In keeping with these results, daily cannabis smoking is a risk factor for fibrosis progression in patients with chronic hepatitis C. In contrast, CB2 display antifibrogenic effects, by a mechanism involving reduction of liver fibrogenic cell accumulation. These results may offer new perspectives for the treatment of liver fibrosis, combining CB2 agonist and CB1 antagonist therapy.

 

[Jarod]

The endocannabinoid system and liver diseases.

Caraceni P, Domenicali M, Bernardi M.
Source

Department of Internal Medicine, Cardioangiology, Hepatology, Alma Mater Studiorum University of Bologna, Bologna, Italy. paolo.caraceni@unibo.it
Abstract

Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules provided by a number of central and peripheral effects, which are mainly mediated by the specific cannabinoid receptors CB(1) and CB(2). Although the expression of these receptors is very low or even absent in the healthy liver, a considerable series of experimental studies and some clinical observations have recognised the EC system as an important player in the pathophysiology of liver diseases. The EC system is highly up-regulated during chronic liver diseases and, to date, it has been implicated in the pathogenesis of non-alcoholic fatty liver disease, progression of fibrosis to cirrhosis and the development of the cardiovascular abnormalities of cirrhosis, such as the hyperdynamic circulatory syndrome and cirrhotic cardiomiopathy. Furthermore, the EC system influences the mechanisms responsible for cell damage and the inflammatory response during acute liver injury, such as that resulting from ischaemia-reperfusion. Thus, molecules targeting the CB(1) and CB(2) receptors may represent potential therapeutic agents for the treatment of liver diseases. At present, the CB(1) antagonists represent the most attractive pharmaceutical tool to resolve fat accumulation in patients with non-alcoholic fatty liver disease and to treat patients with cirrhosis, as they may slow the progression of fibrosis and attenuate the cardiovascular alterations associated with the advanced stage of the disease.

 

[Jarod]

Endocannabinoids in Liver Disease

Joseph Tam, Jie Liu, Bani Mukhopadhyay, Resat Cinar, Grzegorz Godlewski, and George Kunos*

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Abstract

Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and is present both in brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases, which contributes to the underlying pathologies. In cirrhosis of various etiologies, activation of vascular and cardiac CB1 receptors by macrophage- and platelet-derived endocannabinoids contribute to the vasodilated state and cardiomyopathy, which can be reversed by CB1 blockade. In mouse models of liver fibrosis, activation of CB1 receptors on hepatic stellate cells is fibrogenic, and CB1 blockade slows the progression of fibrosis. Fatty liver induced by high-fat diets or chronic alcohol feeding depend on activation of peripheral, including hepatic CB1 receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB1 blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB1 antagonists.

 

[Jarod]

[Endogenous cannabinoids in liver disease: Many darts for a single target].

[Article in Spanish]
Reichenbach V, Ros J, Jiménez W.
Source

Servicio de Bioquímica y Genética Molecular, CIBEREHD, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínico, Universitat de Barcelona, Barcelona, España.
Abstract

Endogenous cannabinoids are ubiquitous lipid-signaling molecules able to partially mimic the actions produced by Delta(9)-tetrahydrocannabinol, the compound responsible for most of the psychological effects of marijuana. Endocannabinoids are derived from arachidonic acid and are involved in many physiological effects. This family of substances includes anandamide (arachidonylethanolamide), 2-arachydonylglycerol, noladin ether and virodhamine. The interaction of these substances with CB1 and CB2 receptors results in most of their biological effects. The endocannabinoid system is involved in the pathogenesis of the cardiovascular dysfunction occurring in advanced liver disease and also plays a role in the pathogenesis of portal hypertension and liver fibrosis. Moreover, this system is also altered in other processes associated with hepatic dysfunction, including encephalopathy, obesity and steatosis. These findings indicate that the endocannabinoid system may open new avenues for the therapeutic regulation of fibrosis and portal hypertension in advanced liver disease.

 

[Jarod]

Cannabinoid receptors as new targets of antifibrosing strategies during chronic liver diseases.

Mallat A, Teixeira-Clerc F, Deveaux V, Lotersztajn S.
Source

INSERM, Unité 841, Institut Mondor de Recherche Biomédicale, Université Paris XII-Val de Marne, Créteil, F-94000, France. Sophie.Lotersztajn@creteil.inserm.fr
Abstract

Chronic liver injury exposes the patient to liver fibrosis and its end stage, cirrhosis, is a major public health problem worldwide. In western countries, prevailing causes of cirrhosis include chronic alcohol consumption, hepatitis C virus infection and non-alcoholic steatohepatitis. Current treatment of hepatic fibrosis is limited to withdrawal of the noxious agent. Nevertheless, suppression of the cause of hepatic injury is not always feasible and numerous efforts are directed at the development of liver-specific antifibrotic therapies. Along these lines, the authors recently demonstrated that the endocannabinoid system shows promise as a novel target for antifibrotic therapy during chronic liver injury. Indeed, cannabinoid receptors CB1 and CB2 promote dual pro- and antifibrogenic effects, respectively. Therefore, endocannabinoid-based therapies, combining CB2 agonists and CB1 antagonists may open novel therapeutic perspectives for the treatment of chronic liver diseases.

 

[Jarod]

Too many more too list.

Pubmed articles on treating liver disease with cannabinoids.....

http://cherrygurl28.com/2012/04/30/cannabis-and-liver-disease/