Tetrahydrocannabinol induces brain mitochondrial respiratory chain dysfunction and increases oxidative stress: a potential mechanism involved in cannabis-related stroke.
Fiche publication
Date publication
janvier 2015
Journal
BioMed research international
Auteurs
Membres identifiés du Cancéropôle Est :
Pr SCHINI-KERTH Valérie, Dr AUGER Cyril
Tous les auteurs :
Wolff V, Schlagowski AI, Rouyer O, Charles AL, Singh F, Auger C, Schini-Kerth V, Marescaux C, Raul JS, Zoll J, Geny B
Lien Pubmed
Résumé
Cannabis has potential therapeutic use but tetrahydrocannabinol (THC), its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities V max (complexes I, III, and IV activities), V succ (complexes II, III, and IV activities), V tmpd (complex IV activity), together with mitochondrial coupling (V max/V 0), were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2) production, measured with Amplex Red. THC significantly decreased V max (-71%; P < 0.0001), V succ (-65%; P < 0.0001), and V tmpd (-3.5%; P < 0.001). Mitochondrial coupling (V max/V 0) was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P < 0.001). Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P < 0.05) and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P < 0.001). Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient's vulnerability to stroke.
Mots clés
Animals, Brain, drug effects, Cannabis, adverse effects, Dronabinol, pharmacology, Electron Transport, drug effects, Free Radicals, metabolism, Hydrogen Peroxide, metabolism, Male, Mitochondria, drug effects, Oxidation-Reduction, drug effects, Oxidative Stress, drug effects, Rats, Wistar, Stroke, chemically induced
Référence
Biomed Res Int. 2015 ;2015:323706