Protection against kainate neurotoxicity by pyrrolidine dithiocarbamate.
The effect of pyrrolidine dithiocarbamate (PDTC) on kainate (KA)-induced neurotoxicity was examined in Sprague-Dawley rats. At 10 mg/kg, i.p., KA produced seizures accompanied by neuronal loss in the hippocampus and increased levels of malondialdehyde (MDA) and protein carbonyl. Pretreatment with PDTC (100 or 200 mg/kg, p.o., every 12 h x 5) blocked KA-induced neurotoxicities (seizures, increases in MDA and protein carbonyl and neuronal losses) in a dose-dependent manner. These effects were counteracted by the adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (25 or 50 micro g/kg, i.p.), but not by the A(2A) receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (0.5 or 1 mg/kg, i.p.) or the A(2B) receptor antagonist alloxazine (1.5 or 3.0 mg/kg, i.p.). Our results suggest that the anticonvulsant and neuroprotective effects of PDTC are mediated, at least in part, via adenosine A(1) receptor stimulation.
Shin
Eun-Joo
EJ
Neurotoxicology Program, College of Pharmacy, Kangwon National University, Chunchon, South Korea.
Jhoo
Jin Hyeong
JH
Kim
Won-Ki
WK
Jhoo
Wang Kee
WK
Lee
Chaeyoung
C
Jung
Bae Dong
BD
Kim
Hyoung-Chun
HC
D000818:Animals; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000473:pathology / Q000517:prevention & control; D013859:Thiocarbamates / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D007608:Kainic Acid