Long-term evaluation of organophosphate toxicity and antidotal therapy in co-cultures of spinal cord and muscle tissue.

Abstract:

:Victims of nerve agents basically require antidotal treatment. There is need for novel antidotes and for therapeutic procedures that are specifically adapted to these patients. To cope with this challenge, in vitro test systems which are easy to handle and allow for conducting long-term studies would be of great benefit. The present work introduces co-cultures of spinal cord and muscle tissue as ex vivo testing systems meeting these criteria. Cell cultures in which functional neuromuscular synapses formed ex vivo were prepared from embryonic mice. Spontaneous muscle activity was recorded by video microscopy. Muscle contractions involved intact neuromuscular transmission as indicated by the effect of succinylcholine, a muscle relaxant that completely abolished muscle activity. At a concentration of 0.75 μM the nerve agent VX reduced the frequency of spontaneous muscle contractions by about 75%. Subsequent application of obidoxime re-established muscle movements. After 24 h of antidotal treatment, muscle activity approached the level of sham-treated cultures and remained stable over the following week. In summary, co-cultures of spinal cord and muscle tissue are promising tools for evaluating the success of antidotal treatment following organophosphate intoxication over a period of at least seven days.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Drexler B,Seeger T,Grasshoff C,Thiermann H,Antkowiak B

doi

10.1016/j.toxlet.2011.04.010

subject

Has Abstract

pub_date

2011-09-25 00:00:00

pages

89-93

issue

1

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(11)00158-5

journal_volume

206

pub_type

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