Papel del sistema endocannabinoides en las enfermedades grasas del hígado y su potencial terapéutico
The role of endocannabinoids system in fatty liver disease and therapeutic potentials.
Alswat KA
Saudi J Gastroenterol [serial online] 2013 [cited 2013 Jul 4];19:144-51.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality with no proven effective therapy as of yet. Its prevalence is increasing globally in parallel with obesity and metabolic syndrome pandemic. The endocannabinoid (EC) system has been implicated in the pathogenesis of several diseases, including fatty liver diseases. This system refers to the cannabinoid receptors type 1 (CB1) and type 2 (CB2), with both their endogenous ligands and machinery dedicated to EC synthesis and degradation. There is accumulating evidence on the role CB1 as a key mediator of insulin resistance and liver lipogenesis in both animals and humans. On the other hand, CB2 receptors have been shown to promote inflammation with anti-fibrogenic properties. The pharmacological modulation of the EC system activity for the treatment of metabolic syndrome and NAFLD are promising yet premature. The initial limited success due to deleterious central nervous system side-effects are likely to be bypassed with the use of peripherally restricted drugs.
Keywords: Cannabinoid receptors type 1, cannabinoid receptors type 2, endocannabinoids, endocannabinoids system, fatty liver disease
http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2013;volume=19;issue=4;spage=144;epage=151;aulast=Alswat
El sistema endocannabinoide como una llave mediadora durante hepatopatías: novedades y posibilidades terapéuticas
The endocannabinoid system as a key mediator during liver diseases: new insights and therapeutic openings.
Mallat A, Teixeira-Clerc F, Deveaux V, Manin S, Lotersztajn S.
INSERM, U955, Créteil, France.
Br J Pharmacol. 2011 Aug;163(7):1432-40. doi: 10.1111/j.1476-5381.2011.01397.x.
Abstract
Chronic liver diseases represent a major health problem due to cirrhosis and its complications. During the last decade, endocannabinoids and their receptors have emerged as major regulators of several pathophysiological aspects associated with chronic liver disease progression. Hence, hepatic cannabinoid receptor 2 (CB(2)) receptors display beneficial effects on alcoholic fatty liver, hepatic inflammation, liver injury, regeneration and fibrosis. Cannabinoid receptor 1 (CB(1)) receptors have been implicated in the pathogenesis of several lesions such as alcoholic and metabolic steatosis, liverfibrogenesis, or circulatory failure associated with cirrhosis. Although the development of CB(1) antagonists has recently been suspended due to the high incidence of central side effects, preliminary preclinical data obtained with peripherally restricted CB(1) antagonists give real hopes in the development of active CB(1) molecules devoid of central adverse effects. CB(2) -selective molecules may also offer novel perspectives for the treatment of liver diseases, and their clinical development is clearly awaited. Whether combined treatment with a peripherally restricted CB(1) antagonist and a CB(2) agonist might result in an increased therapeutic potential will warrant further investigation.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165953/pdf/bph0163-1432.pdf
Endocannabinoides en enfermedades del hígado
Endocannabinoids in liver disease.
Tam J, Liu J, Mukhopadhyay B, Cinar R, Godlewski G, Kunos G.
National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9413, USA.
Hepatology. 2011 Jan;53(1):346-55. doi: 10.1002/hep.24077.
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 it is present in both brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases and contributes to the underlying pathologies. In patients with cirrhosis of various etiologies, the activation of vascular and cardiac CB(1) receptors by macrophage-derived and platelet-derivedendocannabinoids contributes to the vasodilated state and cardiomyopathy, which can be reversed by CB(1) blockade. In mouse models of liverfibrosis, the activation of CB(1) receptors on hepatic stellate cells is fibrogenic, and CB(1) blockade slows the progression of fibrosis. Fatty liverinduced by a high-fat diet or chronic alcohol feeding depends on the activation of peripheral receptors, including hepatic CB(1) receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB(1) blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB(1) antagonists.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073545/pdf/nihms252607.pdf
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Anestesiología y Medicina del Dolor
www.anestesia-dolor.org
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