The Monoacylglycerol Lipase Inhibitor ABX-1431 Does Not Improve Alcoholic Liver Disease.

Abstract

Introduction: Excessive alcohol consumption can result in alcoholic liver disease (ALD). There is no FDA-approved drug to specifically treat ALD and current management approaches have limited efficacy. Past studies indicate that monoacylglycerol lipase (MAGL) inhibition can have a positive impact on nonalcoholic fatty liver disease. However, the effect of MAGL inhibition in ALD has not been reported. Materials and Methods: We tested the highly selective and clinically evaluated MAGL inhibitor ABX-1431 in the Lieber-DeCarli liquid alcohol diet-induced model of ALD in C57BL/6 mice. Results: ABX-1431 failed to reduce ALD-associated steatosis and elevated levels of liver enzymes associated with hepatic injury. Furthermore, survival rate declined with increasing doses of ABX-1431 when compared with mice administered vehicle only. Conclusion: These data suggest that MAGL inhibition does not improve ALD and is unlikely to be a good strategy for this condition.

• Authors: Jennifer L Lucitti, Lucas T Laudermilk, George S Amato, Rangan Maitra
• Journal: Cannabis and cannabinoid research (Cannabis Cannabinoid Res) (May 29 2023) ISSN: 2378-8763 [Electronic] United States
• PMID: 37253145 (Publication Type: Journal Article)