Phytocannabinoids tetrahydrocannabinol and cannabidiol act against rotenone induced damages in murine cell cultures
Phytocannabinoids (PCs) are terpenphenoles deriving from Cannabis species. In the brain, their activity is mediated by specific receptors such as the cannabinoid receptor 1 (CB1) or 2. These receptors are widely expressed in the brain. PCs as well have antioxidative capacities. Since one major event in PD is oxidative stress, cannabinoids are suggested as neuroprotective drugs. Oxidative stress can be induced by the complex I inhibitor rotenone. We investigated the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) on rotenone affected dissociated mesencephalic cultures and neuroblastoma cells (N18TG2) of mice. Cannabinoids (0.1 to 10µM) were administered alone or concomitantly with rotenone (80nM) for 48h. Rotenone treatment resulted in a degeneration of about 20% of the dopaminergic cells which was counteracted significantly by THC and CBD at 10µM. A significant restoration of glutathione levels in rotenone treated cultures at 0.1µM of THC and 10µM of CBD was also found. Electron spin resonance spectroscopy in N18TG2 cells revealed that the amount of superoxide radicals in cells exposed to rotenone nearly doubled. Neither THC nor CBD counteracted this increase. Thus radical scavenging does not appear to be the main mechanism of PCs action. The mechanisms which lead to the observed effects remain to be investigated, but cannabinoids might be candidates for neuroprotective agents in disorders linked to oxidative stress.