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 [A1 antagonist, 8-cyclopentyl-1,3-dimethylxanthine (25 or 50 microg/kg); A2A antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (0.5 or 1 mg/kg); and A2B antagonist, alloxazine (1.5 or 3.0 mg/kg)]. However, this counteraction was most pronounced in the presence of the A1 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.
Kwon
Yong-Soo
YS
Neurotoxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
Park
Dae-Hun
DH
Shin
Eun-Joo
EJ
Kwon
Myung Sang
MS
Ko
Kwang Ho
KH
Kim
Won-Ki
WK
Jhoo
Jin Hyeong
JH
Jhoo
Wang-Kee
WK
Wie
Myung-Bok
MB
Jung
Bae Dong
BD
Kim
Hyoung-Chun
HC
D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005415:Flavins / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D011429:Propolis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000502:physiology*
D058916:Adenosine A1 Receptor Antagonists; D000975:Antioxidants; D005415:Flavins; D043682:Receptor, Adenosine A1; C008173:isoalloxazine; D011429:Propolis; D007608:Kainic Acid