In vitro effects of CB1 receptor ligands on lipid peroxidation and antioxidant defense systems in the rat brain.

The in vitro effects of arachidonyl-2-chloroethylamide (ACEA; a selective CB(1)-receptor agonist) and N-piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-cochlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A; a selective CB(1)-receptor antagonist) on lipid peroxidation (spontaneous and Fe (2+)-induced), total glutathione (GSH)-level and activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and glutathione reductase) in the rat brain were studied. The effects of these CB(1)-induced), total glutathione (GSH)-level and activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and glutathione reductase) in the rat brain were studied. The effects of these CB(1)-ligands in Fenton system (generating *OH radicals) were also examined. The cannabinoids did not change the total GSH-level and were without effects on the activity of antioxidant enzymes in the rat brain. These results proved a lack of in vitro pro-oxidant activity of the CB(1)-receptor ligands, as well as a lack of direct effects on GSH and enzyme molecules. ACEAand SR141716A were without effect on spontaneous lipid peroxidation, but decreased the Fe(2+)-induced brain lipid peroxidation and OH-provoked deoxyribose degradation in Fenton system. It can be suggested that the tested cannabinoids possess a metal-chelating activity, which might contribute to an antioxidant activity. The data, obtained in this study offer a background for investigation of the in vivo effects of these CB(1)-receptor ligands on antioxidant defense systems in the brain of healthy animals and animals, previously subjected to oxidative stress.