Cannabinoid receptors as therapeutic targets in the management of liver diseases.
Despite recent advances in the understanding of mechanisms underlying the pathogenesis of liver diseases, therapeutic agents are still needed in several instances such as nonalcoholic fatty liver disease, alcoholic liver disease or fibrogenesis associated with chronic liver injury. Over the past decades, cannabinoid receptors have emerged as critical mediators of acute and chronic liver injury, and pharmacological modulation of these receptors has demonstrated efficacy in preclinical models of nonalcoholic and alcoholic fatty liver, fibrosis, liver ischemia reperfusion and of complications of cirrhosis, including cirrhotic portal hypertension, cirrhotic cardiomyopathy and hepatic encephalopathy. Moreover, CB(1) antagonists have entered clinical trials for the management of nonalcoholic steatohepatitis. This review will depict the pleiotropic functions of cannabinoid receptors in liver disease and highlight potential therapeutic applications, some of which may be available in the near future.
Mallat
Ariane
A
INSERM, Service d'Hepatologie, Hospital Henri Moudor, Creteil, France. ariane.mallat@hmn.aphp.fr
Lotersztajn
Sophie
S
D000818:Animals; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000502:physiology; D015398:Signal Transduction
D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators; D043882:Receptors, Cannabinoid