Investigation of the effects of KML29, a selective inhibitor of monoacylglycerol lipase (MAGL) on fever induced by lipopolysaccharide (LPS) in rats

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2015
Galioğlu, Fethiye Esin
Endocannabinoid system has recently come into prominence as one of the primary neuromodulatory systems that plays vital roles in sustaining homeostasis. Monoacylglycerol lipase (MAGL) is the main degradation enzyme of the most abundant endocannabinoid found in the brain, 2-arachidonoyl glycerol (2-AG). MAGL is thought to have a potential to exert protective effects on inflammatory states. MAGL serves as a key metabolic node connecting the endocannabinoid and prostaglandin signaling networks and its inhibition causes increase in 2-AG levels and decrease in arachidonic acid levels, both of which may result in remission of inflammation through different mechanisms. In the current study we utilized Lipopolysaccharide (LPS; Escherichia coli O111:B4 250 µg/kg, sc)-administered Wistar albino male rats in order to initiate fever, an inflammatory state mainly generated by the brain and investigated whether injection of KML29 (20 mg/kg, sc), a selective and irreversible inhibitor of MAGL, simultaneously with LPS would alter the fever response by means of a biotelemetric technique. Our results showed that KML29 has a modest but significant ameliorating effect on LPS-induced fever, specifically during the plateau phase. Statistical analysis revealed that the decline in overall temperature change (∆Tab) values of the group whose LPS injection was done simultaneously with KML29 was 1.7 fold less (between 250-600 minutes) compared to the group whose LPS injection was done simultaneously with saline. These results indicate that MAGL activation is an important aspect of physiopathology of inflammation and endogenously increased 2-AG by MAGL inhibiton can lead to protection against fever.
Citation Formats
F. E. Galioğlu, “Investigation of the effects of KML29, a selective inhibitor of monoacylglycerol lipase (MAGL) on fever induced by lipopolysaccharide (LPS) in rats,” M.S. - Master of Science, Middle East Technical University, 2015.