Synthetic cannabinoids and endometrial stromal cell fate: Dissimilar effects of JWH-122, UR-144 and WIN55,212-2

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Fonseca, BM (Author) FFUP; Fernandes, R (Author) Other; Almada, M (Author) Other; Santos, M (Author) Other; Felix Carvalho (Author) FFUP; Teixeira, NA (Author) FFUP; Georgina Correia da Silva (Author) FFUP

Journal

Title: Toxicology

Vol. 413

Pages: 40-47

ISSN: 0300-483X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 8 Citations

Other information

Authenticus ID: P-00P-ZF2

DOI: 10.1016/j.tox.2018.11.006

Abstract (EN): The emergence of synthetic cannabinoids (SCBs) as drugs of abuse in readily available "Spice" smoking blends has exposed users to much more potent cannabinoids than the phytocannabinoids present in Cannabis saliva L. Increasing reports of adverse reactions are emerging in the clinical literature. SCBs may disrupt the endocannabinoid signalling, which has been shown to be crucial within human endometrium remodelling process. Within this study, a telomerase-immortalised human endometrial stromal cell line (St-Tlb) and primary human decidual fibroblasts (HdF) were used to determine the impact of SCBs JWFI-122, UR-144 and WIN55,212-2 (WIN) on endometrial stromal cells. Our findings indicate that JWH-122 and UR-144 (0.01-25 mu M) induce prompt ROS/RNS formation and endoplasmic reticulum (ER) stress without reduction in cell viability. Disturbances in the normal functions of the ER lead to cell stress response, which is after compensated with the increase in reduced/oxidized glutathione ratio (GSH/GSSG). Instead, WIN induces ER stress, mitochondrial dysfunction and apoptotic cell death. The addition of the CBI antagonist AM281 significantly reduces the effects on cell viability, suggesting that CBI plays a key role in WIN-induced apoptosis. Collectively, our data suggests that SCBs have dissimilar effects on human endometrial stromal cells and, thus, may impact human reproductive function through distinct mechanisms that are crucial for the understanding of the pathophysiological outcomes from its abuse.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8