Neuroprotective Effects of Low Dose Anandamide in Pentylenetetrazole-Induced Kindling in Rats
Omar M. E. Abdel-Salam1, Amany A. Sleem2, Marawan Abd El-Baset Mohamed Sayed2, Eman R. Youness3and Nermeen Shaffie4

1Department of Toxicology and Narcotics, National Research Centre, Cairo, Egypt.

2Department of Pharmacology, National Research Centre, Cairo, Egypt.

3Department of Medical Biochemistry, National Research Centre, Cairo, Egypt.

4Department of Pathology, National Research Centre, Cairo, Egypt.

Corresponding Author E-mail: omasalam@hotmail.com

Abstract: Anandamide (N-arachidonoylethanolamine) is an endogenous cannabinoid receptor CB1 ligand that exhibits neuroprotective effects in the brain. In this study, the effect of exogenously given anandamide on pentylenetetrazole (PTZ)-induced chemical kindling oxidative stress and brain damage in rats was studied. Rats were intraperitoneally (i.p.) injected with 35 mg/kg PTZ once every 48 hours for 12 times to induce seizures. Anandamide was i.p. given. 30 min prior to PTZ injection at 100 or 200 mg/kg. Injections of PTZ induced significant increase in brain lipid peroxidation (malondialdehyde: MDA), and nitric oxide associated with marked decrease in brain reduced glutathione (GSH). There were also significant decrements in acetylcholinesterase (AChE) concentration, butyrylcholinesterase (BChE) and paraoxonase-1 (PON-1) activities in brain tissue of PTZ injected rats. Meanwhile, there was no significant effect for PTZ on the concentration of brain neutrophil elastase. Anandamide administered at 100 and 200 mg/kg significantly decreased MDA and increased GSH contents and at 200 mg/kg significantly decreased nitric oxide in brain of PTZ-treated rats. The drug also caused significant increments in AChE concentration and PON-1 activity but had no significant effect on BChE or neutrophil elastase in rats treated with PTZ. Anandamide given at the dose of 200mg/kg significantly decreased the mean seizure scores over the study period by 22.3% and the frequency of myoclonic jerks and rearing (stage 3) by 56.7% compared with the vehicle-treated group. Anandamide given at 100 and 200 mg/kg completely inhibited the development of generalized tonic-clonic seizures (stage 5). It is concluded that in the PTZ-induced seizures, the cannabinoid receptor CB1 agonist anandamide decreases brain oxidative stress, neuronal injury, and exerts an antiepileptic activity.

Keywords: Anandamide; Endocannabinoids; Kindling; Neurodegeneration; Oxidative Stress; Pentylenetetrazole

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