In vivo effects of CB1 receptor ligands on lipid peroxidation and antioxidant defense systems in the rat brain of healthy and ethanol-treated rats

Pharmacol Rep. 2006 Nov-Dec;58(6):876-83.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Arachidonic Acids / pharmacology*
  • Brain / drug effects*
  • Brain / metabolism
  • Ethanol / toxicity*
  • Glutathione / metabolism
  • Ligands
  • Lipid Peroxidation / drug effects*
  • Male
  • Piperidines / pharmacology*
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / physiology*
  • Rimonabant
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Arachidonic Acids
  • Ligands
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • arachidonyl-2-chloroethylamide
  • Ethanol
  • Superoxide Dismutase
  • Glutathione
  • Rimonabant