Objective To investigate the effect of cannabinoid receptor-2 (CB2) agonist AM1241 on nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and interleukin-1β (IL-1β) in liver tissue of mice with acute liver injury induced by concanavalin A (Con-A).
Methods Forty 8-week-old C57BL/6J male mice were randomly divided into a control, a model, and two CB2 receptor agonist (AM1241) groups injected with AM1241 intraperitoneally at doses of 3 and 12 mg/kg one hour before the establishment of acute liver injury model with caudal vein injection of 20 mg/kg Con A in all the mice except for the control mice only with intraperitoneal injection of solvent. Eight hours after the injection of Con A, following indicators were detected for all the mice: serum alanine aminotransferase (ALT); inflammatory body 3 related nucleotide oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 in liver tissues with Western blot; and expression level of interleukin-1 beta (IL-1β) in liver homogenate with enzyme-linked immunosorbent assay (ELISA).
Results Compared to those in the control mice, significantly increased serum ALT (6 132.5 ± 1 300.8 vs. 28.5 ± 7.4 U/L, P < 0.05), NLRP3, ASC, and caspase-1 in liver tissues (P < 0.05 for all) were detected in the model mice. In the mice administered with AMl241, significantly decreased serum ALT (2 696.5 ± 956.3 and 534.6 ± 128.6 U/L, both P < 0.05), NLRP3, ASC and caspase-1 protein in liver tissues (all P < 0.05) were detected in comparison with those in the model mice. Significantly decreased IL-1β in liver homogenate was also detected in the mice with AMl241 treatment compared to that in the control mice (P < 0.05).
Conclusion CB2 receptor agonist AMl241 may have protective effects on Con A-induced acute liver injury in mice and the effects may be related to inhibitions of NLRP3, ASC, caspase-1, and IL-1β expression in liver tissue of mice.
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