20.500.12556/RUL-166740 Exploring the safety of cannabidiol (CBD) a comprehensive in vitro evaluation of the genotoxic and mutagenic potential of a CBD isolate and extract from Cannabis sativa L. Cannabidiol (CBD), a naturally occurring cyclic terpenoid found in Cannabis sativa L., is renowned for its diverse pharmacological benefits. Marketed as a remedy for various health issues, CBD products are utilized by patients as a supplementary therapy or post-treatment failure, as well as by healthy individuals seeking promised advantages. Despite its widespread use, information regarding potential adverse effects, especially genotoxic properties, is limited. The present study is focused on the mutagenic and genotoxic activity of a CBD isolate (99.4 % CBD content) and CBD-rich Cannabis sativa L extract (63.6 % CBD content) in vitro. Both CBD samples were non-mutagenic, as determined by the AMES test (OECD 471) but exhibited cytotoxicity for HepG2 cells (~IC$_{50 (4 h)}$ 26 µg/ml, ~IC$_{50 (24 h)}$ 6–8 µg/ml, MTT assay). Noncytotoxic concentrations induced upregulation of genes encoding metabolic enzymes involved in CBD metabolism, and CBD oxidative as well as glucuronide metabolites were found in cell culture media, demonstrating the ability of HepG2 cells to metabolize CBD. In this study, the CBD samples were found non-genotoxic. No DNA damage was observed with the comet assay, and no influence on genomic instability was observed with the cytokinesis block micronucleus and the γH2AX and p-H3 assays. Furthermore, no changes in the expression of genes involved in genotoxic stress response were detected in the toxicogenomic analysis, after 4 and 24 h of exposure. Our comprehensive study contributes valuable insights into CBD’s safety profile, paving the way for further exploration of CBD’s therapeutic applications and potential adverse effects. cannabidiol CBD metabolism cytotoxicity genotoxicity mutagenicity kanabidol CBD izvleček Cannabis sativa L. varnost genotoksičnost true false true Angleški jezik Slovenski jezik Članek v reviji 2025-01-23 13:47:48 2025-01-23 13:47:53 2025-01-24 04:05:30 0000-00-00 00:00:00 2024 0 0 13 str. art. 116969 Vol. 177 Aug. 2024 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 615.9 1950-6007 10.1016/j.biopha.2024.116969 200108803 1-s2.0-S0753332224008539-main.pdf 1-s2.0-S0753332224008539-main.pdf 1 02528FB9E51FDB0CC14CF41141806AD8 a5a46d4927f332330aef94f70b38482cbad7ad97d57890d66bd74f019a68eec0 c6eaadeb-d987-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=198578 https://www.sciencedirect.com/science/article/pii/S0753332224008539 1 787472b2-d987-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=198577 Fakulteta za farmacijo Biotehniška fakulteta 0 0 0