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PROTECTION AGAINST KAINATE NEUROTOXICITY BY PYRROLIDINE DITHIOCARBAMATE
Author(s) -
Shin EunJoo,
Jhoo Jin Hyeong,
Kim WonKi,
Jhoo Wang Kee,
Lee Chaeyoung,
Jung Bae Dong,
Kim HyoungChun
Publication year - 2004
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2004.03990.x
Subject(s) - neurotoxicity , pyrrolidine dithiocarbamate , chemistry , antagonist , receptor antagonist , pharmacology , malondialdehyde , adenosine a2a receptor , kainic acid , kainate receptor , adenosine receptor , medicine , receptor , endocrinology , agonist , biochemistry , glutamate receptor , toxicity , antioxidant , ampa receptor , signal transduction , nf κb , organic chemistry
Summary 1. The effect of pyrrolidine dithiocarbamate (PDTC) on kainate (KA)‐induced neurotoxicity was examined in Sprague‐Dawley rats. 2. 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. 3. Pretreatment with PDTC (100 or 200 mg/kg, p.o., every 12 h ×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 µg/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.). 4. Our results suggest that the anticonvulsant and neuroprotective effects of PDTC are mediated, at least in part, via adenosine A 1 receptor stimulation.