The Effect of CB1 Antagonism on Hepatic Oxidative/Nitrosative Stress and Inflammation in Nonalcoholic Fatty Liver Disease

(E-pub Ahead of Print)

Author(s): Bojan Jorgačević, Danijela Vučević, Janko Samardžić, Dušan Mladenović, Milena Vesković, Dušan Vukićević, Rada Ješić, Tatjana Radosavljević*.

Journal Name: Current Medicinal Chemistry

Abstract:

Dysfunction of the endocannabinoid system ( ES ) has been identified in nonalcoholic fatty liver disease (NAFLD) and associated metabolic disorders. Cannabinoid receptor 1 (CB1) expression is largely dependent on nutritional status. Thus, individuals suffering from NAFLD and metabolic syndrome (MS) have a significant increase in ES activity. Furthermore, oxidative/nitrosative stress and inflammatory process modulation in the liver is highly influenced by the ES. Numerous experimental studies indicate that oxidative and nitrosative stress in the liver are associated with steatosis and portal inflammation during NAFLD. On the other hand, inflammation itself may also contribute to reactive oxygen species (ROS) production due to Kupffer cell activation and increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The pathways by which endocannabinoids and their lipid-related mediators modulate oxidative stress and lipid peroxidation represents a significant area of research that could yield novel pharmaceutical strategies for the treatment of NAFLD. Cumulative evidence suggested that the ES, particularly CB1 receptors, may also play a role in inflammation and disease progression toward steatohepatitis. Pharmacological inactivation of CB1 receptors in NAFLD exerts multiple beneficial effects, particularly due to the attenuation of hepatic oxidative/nitrosative stress parameters and a significant reduction of proinflammatory cytokine production. However, further investigations regarding precise mechanisms by which CB1 blockade influences reduction of hepatic oxidative/nitrosative stress and inflammation are required before moving toward clinical investigation.

Keywords: NAFLD, Endocannabinoids, CB1 antagonism, Oxidative/nitrosative stress, Inflammation, CB receptors

Rights & PermissionsPrintExport Cite as


Article Details

(E-pub Ahead of Print)
DOI: 10.2174/0929867327666200303122734
Price: $95