Praoxon-induced changes in the function of chicken biventer cervices nerve-muscle preparation and the reversal of such changes by pralidoxime

Abstract

One of the most toxic effects of organophosphate (OP) poisoning has been the paralysis of skeletal muscles that can lead to paralysis of respiratory muscles and death. However, oximes are the only antidotes available to reverse or prevent such toxic effects of OP insecticides and nerve chemical warfare agents. In the present research work, the effect of different concentrations of paraoxon (as an OP) on the function of skeletal muscle and reversal or prevention of these effects by an oxime (pralidoxime, 2-PAM) were studied in chicken biventer cervices nerve-muscle preparation using twitch tension recording technique. For this purpose, twitches of the biventer cervices 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 and contractures were recorded isotonically using Narco Biosystems. The results showed that paraoxon (10 nM) induces a significant increase (more than 100%) in the twitch amplitude, while higher concentrations (30 and 100 nM) could induce partial or total contractures. In this study, paraoxon at a concentration of 10 nM was used to examine the capability of pralidoxime to reverse or prevent its effects. Pralidoxime at doses of 300 and 100 µM 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. While oxime at doses of 30 and 10 µM could only reverse or reduce this effect to about 25 and 70% respectively, pralidoxime alone had no significant effect on the function of the muscle. These results suggest that this applied method is of high value in studying the functional effects of OPs on skeletal muscle tissues and the reversal effects of antidotes, and pralidoxime by itself may fully reverse such effects.