Cannabinoid receptor type 2 agonist JWH-133 deteriorates the liver toxicity induced by cypermethrin

Abstract

Cannabinoid receptor 2 (CB2) has a role in the pathology of some liver diseases. Cypermethrin (CYP) is a synthetic pyrethroid insecticide used commonly for the control of pests and vectors, and for protection of foodstuffs. In this study, the involvement of CB2 in CYP-induced liver damage in rats was investigated. CYP was applied to rats orally at a dose of 125 mg/kg bw per day for 14 days. CB2 agonist JWH-133 was administered by intraperitoneal injection at a dose of 3 mg/kg bw per day for the last 4 days of CYP toxicity. JWH-133 deteriorated the liver damage induced by CYP. JWH- 133 increased serum hepatic enzyme activities (aspartate aminotransferase, alanine aminotransferase) in rats given CYP. However, it decreased lipid peroxidation. There were no differences in the levels of hepatic CB2 mRNA among the groups. CB2 receptors were expressed in a small amount in normal liver tissue. In contrast, the expression levels of CB2 in CYPtreated rats were increased in fibrocyte/fibroblast, bile duct epithelial cells, Kupffer cells, and mast cells. In conclusion, CB2 was upregulated in the liver exposed to CYP, predominantly in hepatic fibrogenic cells. JWH-133 enhanced the CYPinduced liver damage by receptor mediated and/or nonreceptor-mediated mechanisms. CB2 antagonists may reduce the damage. The results of the study show that CB2 might be involved in the physiopathological process of CYP-induced liver injury and justify the need for further study.