Metabolites of Cannabis Induce Cardiac Toxicity and Morphological Alterations in Cardiac Myocytes.

Autor: Merve AO; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, London KT1 2EE, UK., Sobiecka P; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, London KT1 2EE, UK., Remeškevičius V; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, London KT1 2EE, UK., Taylor L; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, London KT1 2EE, UK., Saskoy L; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, London KT1 2EE, UK., Lawton S; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, London KT1 2EE, UK., Jones BP; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, London KT1 2EE, UK., Elwakeel A; Centre for Sport, Exercise and Life Sciences (CSELS), Coventry University, Pharmacology and Therapeutics, Alison Gingell Building, Whitefriars Street, Coventry CV1 2DS, UK., Mackenzie FE; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, London KT1 2EE, UK., Polycarpou E; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, London KT1 2EE, UK., Bennett J; Centre for Sport, Exercise and Life Sciences (CSELS), Coventry University, Pharmacology and Therapeutics, Alison Gingell Building, Whitefriars Street, Coventry CV1 2DS, UK., Rooney B; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, London KT1 2EE, UK.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Jan 26; Vol. 23 (3). Date of Electronic Publication: 2022 Jan 26.
DOI: 10.3390/ijms23031401
Abstrakt: Cannabis is one of the most commonly used recreational drugs worldwide. Rrecent epidemiology studies have linked increased cardiac complications to cannabis use. However, this literature is predominantly based on case incidents and post-mortem investigations. This study elucidates the molecular mechanism of Δ9-tetrahydrocannabinol (THC), and its primary metabolites 11-Hydroxy-Δ9-THC (THC-OH) and 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THC-COOH). Treatment of cardiac myocytes with THC-OH and THC-COOH increased cell migration and proliferation ( p < 0.05), with no effect on cell adhesion, with higher doses (250-100 ng/mL) resulting in increased cell death and significant deterioration in cellular architecture. Conversely, no changes in cell morphology or viability were observed in response to THC. Expression of key ECM proteins α-SMA and collagen were up-regulated in response to THC-OH and THC-COOH treatments with concomitant modulation of PI3K and MAPK signalling. Investigations in the planarian animal model Polycelis nigra demonstrated that treatments with cannabinoid metabolites resulted in increased protein deposition at transection sites while higher doses resulted in significant lethality and decline in regeneration. These results highlight that the key metabolites of cannabis elicit toxic effects independent of the parent and psychoactive compound, with implications for cardiotoxicity relating to hypertrophy and fibrogenesis.
Databáze: MEDLINE
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