TY - JOUR
T1 - Circulating and hepatic endocannabinoids and endocannabinoid-related molecules in patients with cirrhosis
AU - Caraceni, Paolo
AU - Viola, Antonella
AU - Piscitelli, Fabiana
AU - Giannone, Ferdinando
AU - Berzigotti, Annalisa
AU - Cescon, Matteo
AU - Domenicali, Marco
AU - Petrosino, Stefania
AU - Giampalma, Emanuela
AU - Riili, Anna
AU - Grazi, Gianluca
AU - Golfieri, Rita
AU - Zoli, Marco
AU - Bernardi, Mauro
AU - Di Marzo, Vincenzo
PY - 2010
Y1 - 2010
N2 - Background/Aims: Endocannabinoids include anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Endocannabinoid-related molecules like oleoyl-ethanolamine (OEA) and palmitoyl-ethanolamine (PEA) have also been identified. AEA contributes to the pathogenesis of cardiovascular alterations in experimental cirrhosis, but data on the endocannabinoid system in human cirrhosis are lacking. Thus, we aimed to assess whether circulating and hepatic endocannabinoids are upregulated in cirrhotic patients and whether their levels correlate with systemic haemodynamics and liver function. Methods: The endocannabinoid levels were measured in peripheral and hepatic veins and liver tissue by isotope-dilution liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. Systemic haemodynamics were assessed by the transthoracic electrical bioimpedance technique. Portal pressure was evaluated by hepatic venous pressure gradient. Results: Circulating AEA and, to a greater extent, PEA and OEA were significantly higher in cirrhotic patients than in controls. PEA and OEA were also increased in the cirrhotic liver tissue. AEA, OEA and PEA levels were significantly higher in peripheral than in the hepatic veins of cirrhotic patients, while the opposite occurred for 2-AG. Finally, circulating AEA, OEA and PEA correlated with parameters of liver function, such as serum bilirubin and international normalized ratio. No correlations were found with systemic haemodynamics. Conclusions: The endocannabinoid system is upregulated in human cirrhosis. Peripheral AEA is increased in patients with a high model of end-stage liver disease score and may reflect the extent of liver dysfunction. In contrast, the 2-AG levels, the other major endocannabinoid, are not affected by cirrhosis. The upregulation of the endocannabinoid-related molecules, OEA and PEA, is even greater than that of AEA, prompting pharmacological studies on these compounds.
AB - Background/Aims: Endocannabinoids include anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Endocannabinoid-related molecules like oleoyl-ethanolamine (OEA) and palmitoyl-ethanolamine (PEA) have also been identified. AEA contributes to the pathogenesis of cardiovascular alterations in experimental cirrhosis, but data on the endocannabinoid system in human cirrhosis are lacking. Thus, we aimed to assess whether circulating and hepatic endocannabinoids are upregulated in cirrhotic patients and whether their levels correlate with systemic haemodynamics and liver function. Methods: The endocannabinoid levels were measured in peripheral and hepatic veins and liver tissue by isotope-dilution liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. Systemic haemodynamics were assessed by the transthoracic electrical bioimpedance technique. Portal pressure was evaluated by hepatic venous pressure gradient. Results: Circulating AEA and, to a greater extent, PEA and OEA were significantly higher in cirrhotic patients than in controls. PEA and OEA were also increased in the cirrhotic liver tissue. AEA, OEA and PEA levels were significantly higher in peripheral than in the hepatic veins of cirrhotic patients, while the opposite occurred for 2-AG. Finally, circulating AEA, OEA and PEA correlated with parameters of liver function, such as serum bilirubin and international normalized ratio. No correlations were found with systemic haemodynamics. Conclusions: The endocannabinoid system is upregulated in human cirrhosis. Peripheral AEA is increased in patients with a high model of end-stage liver disease score and may reflect the extent of liver dysfunction. In contrast, the 2-AG levels, the other major endocannabinoid, are not affected by cirrhosis. The upregulation of the endocannabinoid-related molecules, OEA and PEA, is even greater than that of AEA, prompting pharmacological studies on these compounds.
KW - Cirrhosis
KW - Endocannabinoids
KW - Liver dysfunction
KW - Portal hypertension
KW - Systemic haemodynamics
UR - http://www.scopus.com/inward/record.url?scp=77954375662&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954375662&partnerID=8YFLogxK
U2 - 10.1111/j.1478-3231.2009.02137.x
DO - 10.1111/j.1478-3231.2009.02137.x
M3 - Article
C2 - 19840245
AN - SCOPUS:77954375662
SN - 1478-3223
VL - 30
SP - 816
EP - 825
JO - Liver International
JF - Liver International
IS - 6
ER -