In vivo effects of CB1 receptor ligands on lipid peroxidation and antioxidant defense systems in the rat brain of healthy and ethanol-treated rats.
In vivo experiments were conducted to study the effects of N-(piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-cochlo-rophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A; a potent and selective CB(1)-receptor antagonist) and ara-chidonyl-2-chloroethylamide (ACEA; a selective CB(1)-receptor agonist) on spontaneous lipid peroxidation, glutathione (GSH) level and activities of antioxidant enzymes in rat tissues. Single doses of SR141716A(3 mg/kg, ip) and ACEA(10 mg/kg, ip) had no effect on all indices, studied in the brain, except for a decrease in GSH level by 10 mg/kg of SR141716A. The effects of repeated administration of the CB(1)-receptor ligands (3 mg/kg, ip, once daily for 2 days) on the above indices in the brain and liver of control and ethanol-treated animals were also studied. Two weeks after ethanol exposure, the rats lost weight (by 41%), which correlated with their decreased water and food consumption (by 52% and 33%, respectively). The time of ethanol action was not sufficient to change the biochemical parameters in the brain, except for the lipid peroxidation. However, a decrease in GSH level and superoxide dismutase activity, as well as an increase in lipid peroxidation and glucose-6-phosphate dehydrogenase activity were registered in the liver. The repeated administration of CB(1) receptor ligands restored some of ethanol-induced changes. The present results suggested lack of pro-oxidant activity and potential antioxidant ability of the studied CB(1) receptor ligands, which might contribute to their beneficial effects.
Tsvetanova
Elina
E
Institute of Physiology, Bulgarian Academy of Sciences, 23 Acad. G. Bonchev St., 1113 Sofia, Bulgaria.
Kessiova
Mila
M
Alexandrova
Albena
A
Petrov
Lubomir
L
Kirkova
Margarita
M
Todorov
Simeon
S
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001095:Arachidonic Acids / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D008024:Ligands; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D000077285:Rimonabant; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D001095:Arachidonic Acids; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C119325:arachidonyl-2-chloroethylamide; D000431:Ethanol; D013482:Superoxide Dismutase; D005978:Glutathione; D000077285:Rimonabant