Safety assessment and redox status in rats after chronic exposure to cannabidiol and cannabigerol. (April 2023)

• Record Type: Journal Article
• Authors: Polanska, Hana Holcova; Petrlakova, Katerina; Papouskova, Barbora; Hendrych, Michal; Samadian, Amir; Storch, Jan; Babula, Petr; Masarik, Michal; Vacek, Jan
• Is Part Of: Toxicology. Volume 488(2023)
• Publication Date: 2023-04
• Subjects: CAN acetonitrile -- ALT alanine transaminase -- CBD cannabidiol -- CBG cannabigerol -- CE collision energy -- DCF 2′, 7′-dichlorofluorescein -- GI gastro-intestinal -- HPLC high-performance liquid chromatography -- MDA malondialdehyde -- MRM multiple reaction monitoring -- MS mass spectrometry -- NF kappa B nuclear factor kappa B -- OECD Organisation for Economic Co-operation and Development -- ROS reactive oxygen species -- THC delta-9-tertrahydrocannabinol -- UV ultra-violet; Phytocannabinoid -- in vivo experiment -- Antioxidant -- CBD protective properties -- CBG toxicity; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2023.153460
• Languages: English
• ISSNs: 0300-483X

Abstract

Abstract: Cannabidiol (CBD) and cannabigerol (CBG) are the two main non-psychotropic phytocannabinoids with high application potential in drug development. Both substances are redox-active and are intensively investigated for their cytoprotective and antioxidant action in vitro . In this study, we focused on an in vivo safety evaluation and the effect of CBD and CBG on the redox status in rats in a 90-d experiment. The substances were administered orogastrically in a dose of 0.66 mg synthetic CBD or 0.66 mg/1.33 mg CBG/kg/day. CBD produced no changes in the red or white blood count or biochemical blood parameters in comparison to the control. No deviations in the morphology or histology of the gastrointestinal tract and liver were observed. After 90 d of CBD exposure, a significant improvement in redox status was found in the blood plasma and liver. The concentration of malondialdehyde and carbonylated proteins was reduced compared to the control. In contrast to CBD, total oxidative stress was significantly increased and this was accompanied by an elevated level of malondialdehyde and carbonylated proteins in CBG-treated animals. Hepatotoxic (regressive changes) manifestations, disruption in white cell count, and alterations in the ALT activity, level of creatinine and ionized calcium were also found in CBG-treated animals. Based on liquid chromatography-mass spectrometry analysis, CBD/CBG accumulated in rat tissues (in the liver, brain, muscle, heart, kidney and skin) at a low ng level per gram. Both CBD and CBG molecular structures include a resorcinol moiety. In CBG, there is an extra dimethyloctadienyl structural pattern, which is most likely responsible for the disruption to the redox status and hepatic environment. The results are valuable to further investigation of the effects of CBD on redox status and should contribute towards opening up critical discussion on the applicability of other non-psychotropic cannabinoids. Graphical Abstract: ga1 Highlights: Cannabidiol (CBD) and cannabigerol (CBG) prepared synthetically were investigated in vivo . The effect of CBD and CBG on safety and redox status in rats was evaluated. CBD improved redox status in rats after chronical exposure to a low dose of 0.66 mg/kg/day. CBG ingestion manifested as hepatotoxic effects and redox status disruption. CBD working as cytoprotectant and antioxidant after 90-d subchronic exposure in animals.