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

Dysfunction of the endocannabinoid system (ES) has been identified in nonalcoholic fatty liver disease (NAFLD) and associated metabolic disorders. Cannabinoid receptor type 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 are highly influenced by the ES. Numerous experimental studies indicate that oxidative and nitrosative stress in the liver is asso ciated 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 represent 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 significant reduction of proinflammatory cytokine production. However, further investigations regarding precise mechanisms by which CB1 blockade influences the reduction of hepatic oxidative/nitrosative stress and inflammation are required before moving toward the clinical phase of the investigation.

Automated summary

Dysfunction of the endocannabinoid system has been linked to nonalcoholic fatty liver disease and metabolic disorders, affecting oxidative stress and inflammation in the liver. Research suggests that modulation of endocannabinoids may lead to novel pharmaceutical strategies for treating NAFLD, with potential benefits in reducing oxidative stress and inflammation in the liver. Further investigation is needed to understand the precise mechanisms by which targeting CB1 receptors can influence hepatic oxidative stress and inflammation before clinical application.