اثر مقادير تحت كشنده گاز خردل بر روي آنزيم استيل كولين استراز در آزمايشات درون تن و برون تن

In vitro and in vivo effects of sublethal doses of sulfur mustard on acetylcholine esterase

Even half century after the first use of sulfur mustard as a chemical weapon, it is still being used occasionally in regional and international conflicts. Sulfur mustard is a non-selective alkylating agent, which has been used as chemical warfare many times in last decades. It has devastating effects on numerous tissues and biomolecules and could cause painful death after exposure to its lethal doses. One of the most important enzymes which may be affected by sulfur mustard is acetylcholine esterase (AchE), enzyme responsible for cleavage of acetylcholine and termination of its effect in cholinergic nerve system. The enzyme is the main target for organophosphate and carbamate pesticides. To evaluate the effects of sublethal doses of sulfur mustard on AchE, 500 microlitter of purified serum AchE in phosphate buffer incubated with different concentrations of sulfur mustard at 25"C for 10 min. Determination of enzyme showed a significant reduction of enzyme activity. Also to evaluate effect of oximes on recovery of sulfur ustard inhibited AchE, pralidoxime has been used both before and after incubation. Intraperitonal injections of 5 and 10 mg/kg of sulfur mustard significantly reduced AchE activity in serum, muscles and RBCs. However, the reduction ofAchE activity in the liver and brain was not significant. The results of the study indicate that sulfur mustard even in sublethal doses significantly inhibits AchE. However, mechanism of inhibition is different from that of organophosphate pesticides.