Antioxidant propolis attenuates kainate-induced neurotoxicity via adenosine A₁ receptor modulation in the rat

We examined the effects of the antioxidant propolis on seizures induced by kainic acid (KA). Sprague-Dawley rats received propolis (75 and 150 mg/kg, p.o.) five times at 12 h intervals. KA (10 mg/kg, i.p.) was injected 1 h after the last propolis treatment. Pretreatment with propolis significantly attenuated KA-induced seizures and KA-induced increases in hippocampal AP-1 DNA binding activity in a dose-dependent manner. KA induced increases in the levels of malondialdehyde and protein carbonyl, and a decrease in the ratio of GSH/GSSG. These oxidative stresses and neuronal degenerations were significantly attenuated by pretreatment with propolis. The neuroprotective effects of propolis appeared to be counteracted by adenosine receptor antagonists [A ₁ antagonist, 8-cyclopentyl-1,3-dimethylxanthine (25 or 50 μg/kg) ; A_2A antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (0.5 or 1 mg/kg); and A_2B antagonist, alloxazine (1.5 or 3.0 mg/kg)]. However, this counteraction was most pronounced in the presence of the A ₁ antagonist. Our results suggest that the protective effect of propolis against KA-induced neurotoxic oxidative damage is, at least in part, via adenosine A₁ receptor modulation.