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Organophosphate-induced brain injuries: delayed apoptosis mediated by nitric oxide.

Abstract：

:The features of organophosphate-induced brain injuries were investigated. Rats were 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 diisopropylfluorophosphate treatment predominently in hippocampus and piriform/entorhinal cortices, showing a spongiform 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 to 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 part through nitric oxide production.

journal_name

Environ Toxicol Pharmacol

journal_title

Environmental toxicology and pharmacology

authors

Kim YB,Hur GH,Shin S,Sok DE,Kang JK,Lee YS

doi

10.1016/s1382-6689(99)00006-x

subject

Has Abstract

pub_date

1999-04-01 00:00:00

pages

147-52

issue

2

eissn

1382-6689

issn

1872-7077

pii

S1382-6689(99)00006-X

journal_volume

7

pub_type

杂志文章

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