کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2599949 1133242 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Restoration of nerve agent inhibited muscle force production in human intercostal muscle strips with HI 6
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Restoration of nerve agent inhibited muscle force production in human intercostal muscle strips with HI 6
چکیده انگلیسی

An important factor for successful therapy of poisoning with organophosphorus compounds (OP) is the rapid restoration of blocked respiratory muscle function. To achieve this goal, oximes are administered for reactivation of inhibited acetylcholinesterase (AChE). Unfortunately, clinically used oximes, e.g. obidoxime and pralidoxime, are of limited effectiveness in poisoning with different OP nerve agents requiring the search for alternative oximes, e.g. HI 6. In view of substantial species differences regarding reactivation properties of oximes, the effect of HI 6 was investigated with sarin, tabun and soman exposed human intercostal muscle. Muscle force production by indirect field stimulation and the activity of the human muscle AChE was assessed. 30 μM HI 6 resulted in an almost complete recovery of sarin blocked muscle force and in an increase of completely inhibited muscle AChE activity to approx. 30% of control. In soman or tabun exposed human intercostal muscle HI 6 (50 and 100 μM) had no effect on blocked muscle force or on inhibited human muscle AChE activity. In addition, HI 6 up to 1000 μM had no effect on soman blocked muscle force indicating that this oxime has no direct, pharmacological effect in human tissue. These results emphasize that sufficient reactivation of AChE is necessary for a beneficial therapeutic effect on nerve agent blocked neuromuscular transmission.


► Restoration of nerve agent paralysed human muscle force by HI 6 was investigated.
► HI 6 restored sarin blocked muscle force at clinical relevant concentrations.
► Force recovery was accompanied by reactivation of inhibited acetylcholinesterase.
► In soman or tabun poisoning no reactivation was possible.
► In soman or tabun poisoning no restoration of blocked muscle force occurred.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 206, Issue 1, 25 September 2011, Pages 72–76
نویسندگان
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