The effect of HI-6 on reversal or prevention of changes induced by paraoxon in the function of Chicken biventer cervices nerve-muscle preparation



Paralysis of skeletal muscles, which can lead to paralysis of respiratory muscles and death, is one of the most toxic effects of organophosphates, and oximes are almost the only known antidotes that can reverse or prevent such toxic effects. In the present research work, possible reversal or preventive effect of different concentrations of the relatively new oxime (HI-6) on changes induced by paraoxon on the function of skeletal muscle were studied in chicken biventer cervices nerve-muscle (CBC) preparation using twitch tension recording technique. For this purpose, twitches of the CBC muscle were evoked by stimulating the motor nerve at 0.1 Hz with pulses of 0.2 msec duration and a voltage of greater than that required to produce the maximum response. Twitches were recorded isotonically using Narco Biosystems. Our prior findings revealed that paraoxon at a concentration of 10 nM induces a significant increase (more than 100%) in the twitch amplitude, and therefore, this concentration was used to examine the efficacy of HI-6 to reverse or prevent such effects. HI-6 at 1000 µM could almost fully reverse (when it was used as post treatment) or prevent (when it was used as pretreatment or at the same time as toxin) the effect of paraoxon. It could also reverse or reduce this effect to about 25, 50 and 75% at 300, 100 and 30 µM respectively. Furthermore, HI-6 at 10 µM produced no significant preventive or reversal effect. However, HI-6 alone at 1000 µM increased the twitch amplitude by about 20%. These data indicated that HI-6 could be recognized as an antidote of paraoxon, although it may have other effects at high concentrations.