Therapeutic And Preventive Effects Of Benthiactzine Against Respiratory Failure Induced By Cholinesterase Inhibitor DDVP In Rats

Medical scientists both in civilian and military always pay close attention to the intoxication of cholinesterase inhibitors (ChEI). There are about 80,000 victims caused by organophosphate insecticides every year in China. Most victims are died from circulatory failure, respiratory failure or convulsion. The death rate is about 10% per year in China. Accordingly, it is of significant virtual importance to search for an innovative and effective medicine against poisoning..The intoxication of cholinesterase inhibitor induced by the inhibition of central choline esterase, then M-receptors and N-receptors are agitated by the acetylcholine. In the past, more attention was put on the muscarinic receptor antagonism, and the nicotinic receptor antagonism was negated. Recent studies show that neuronal nicotinic acetylcholine receptors play a role in the process of the cholinesterase inhibitor poisoning.Based on the theory, Benthiactzine, a derivant of benzilic acid, was designed and synthesized at our institute. It has antagonism of both muscarinic and nicotinic acetylcholine receptors. Our earlier studies showed favourable effect on circulatory failure caused by ChEI, which have established that benthiactzine exhibits strong characteristics and has potential therapeutic advantages for future application in the treatment of the intoxication of cholinesterase inhibitor.There are 2 sections in our study. In the first section, we made the acute respiratory failure model in rats, then benthiactzine was injected The therapeutic effects of benthiactzine against DDVP poisoning rats were valued in this section. In the second section, the rats were injected with benthiactzine first, then the DDVP poisoning symptoms were observed. The objective is to value the preventive effects of benthiactzine against DDVP poisoning rats in this section. In the first section, the respiratory failure rats were induced successfully by DDVP, cyanosis and convulsion were occurred in all groups. The rats of benthiactzine treating groups were recovered in 5 min after treatment and returned to normal statue in 30 min. The cure rate in 3 benthiactzine groups were 66.7%,77.8%and 88.9%。The respiratory rate also returned to normal statue in 30 min. In respiratory failure, PaO2 and SaO2 were decreased; resulting in mixed acidosis. 30 min after the treatment of benthiactzine, PaO2 and SaO2 were returned to normal level; PH,PaCO2 and HCO3ˉwere also returned to normal. Serum SOD in respiratory failure were decreased than that of before poisoning and increased after 30 min after the treatment. Serum MDA in respiratory failure rats were increased than that of before poisoning and returned to normal after 30 min after the treatment. In respiratory failure rats, the lung tissue slides with HE staining showed that the pulmonary vessels being dilated and filled with erythrocytes, pulmonary intervals became wide and red blood cells could be seen in alveolar and bronchial cavities, and many inflammatory cells accumulated, pulmonary edema and hemorrhage appeared. The rats treated with benthiactzine had a better signs. Conclusions Treated with benthiactzine, DDVP poisoning rats can get away from respiratory failure in a short time. Benthiactzine can be a favourable medicine against respiratory failure induced by organophoorus pesticides to save time for other clinic treatments.In the second section, the control rats were dead within 3-5 min with symptoms of fasciculation, cynosis and convulsion et al. The benthiactzine preventive rats showed mild N symptoms such as fasciculation and weakness, then recovery to normal. The blood gas analysis is of no difference from before and after poisoning. The lung tissue slides of dead rat with HE staining showed that the pulmonary vessels being dilated and filled with erythrocytes, pulmonary intervals became wide and red blood cells could be seen in alveolar and bronchial cavities, and many inflammatory cells accumulated, pulmonary edema and hemorrhage appeared. The lung tissue of rats with preventive benthiactzine is normal. Conclusions: Benthiactzine can be used to prevent rats from respiratory failure induced by organophoorus pesticides.