KMID : 0614019990150010289
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Journal of Pharmaceutical Sciences (C.N.U.) 1999 Volume.15 No. 1 p.289 ~ p.294
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Organophosphate-induced brain injuries
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Kim Yun-Bae
Hur Gyeung-Haeng Shin Sung-Ho Sok Dai-Eun Kang Jong-Koo Lee Yong-Soon
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Abstract
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The features of organophosphate-induced brain injuries were investigated. Rats was poisoned intraperitoneally with 9 mg/kg (1.8 LD_50) of diisopropylfluorophosphate, Pyridostigmine bromide (0.1 mg/kg) and atropine methylnitrate (20 mg/kg), which are centrally inactive, were pre-treated intramuscularly to reduce the mortality and eliminate peripheral signs. Diisopropylfluorophosphate induced severe limbic seizures. and early necrotic and delayed apoptotic brain injuries. The necrotic brain injury was observed to be maximal as early as 1 h after diisopropvlftuorophosphate treatment predominently in hippocampus and piriform entorhinal cortices. showing a spongifonn change (malacia) of neuropils in severe cases. In contrast, typical apoptotic (TUNEL-positive) cells started to appear at 12 h in thalamus, and a mixed type in amygdala, Separately. nitrite/nitrate content in cerebrospinal fluid was found 10 significantly increase after 2 h, reaching a maximal level at 6 h, Pre-treatment with L-N^G-nitroarginine, an inhibitor of nitric oxide synthase, reduced nitrite/nitrate content and. noteworthy, attenuated only apoptotic brain injury in all four brain regions without affecting seizure intensity and necrotic injury. Taken together, the delayed apoptotic injury of brain induced by diisopropylfluorophosphate poisoning in rats might be mediated in pan through nitric oxide production.
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KEYWORD
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Diisopropylfluorophosphate, Seizures, Brain injury, Terminal deoxynucleotidyl transferase-mediated d-UTP nick end labeling (TUNEL), Nitric oxide
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