P-295 - Prooxidant effects of synthetic cannabinoids on endometrial cells, results in a strenous rebound adaptative effect

Abstract

Synthetic cannabinoids (SCs) are easily available and their use as recreational drugs has increased over the years. It is known that the endocannabinoid system plays an important role in early pregnancy. Here, we assessed whether the chronic exposure (24, 48 and 72 h) to SCs JWH-018, JWH-122, UR-144, THJ-2201, 5F-PB-22 and AB-FUBINACA (0.01–25 µM) may affect human primary decidual fibroblasts (HdF) and endometrial stromal cell line (St-T1b) viability and redox status. For cell proliferation/viability we used MTT, ATP and BrDU assays, whereas redox status was analysed through detection of reactive oxygen species (ROS) and of reduced glutathione (GSH). Exposure to SCs caused an increase in mitochondrial activity, as indicated by MTT assay and ATP production, although no changes were seen in BrDU or in the ratio between mitochondrial and nuclear DNA. In addition, these compounds induced a prompt ROS/RNS release independently of either CB1 or CB2 receptors. On the other hand, chronic exposure (48 h) with JWH -018, JWH-122 and UR-144, revealed a reduction in ROS species generation accompanied by an increase in GSH, mostly in HdF cells. Collectively, our data suggests that SCs improve the antioxidant status of the endometrial cells, only after 48 h, in reaction to SCs initial aggression.