Molecular docking analysis of acetylcholinesterase corroborates the protective effect of pralidoxime against chlorpyrifos-induced behavioral and neurochemical impairments in Nauphoeta cinerea

Toxic organophosphates (OPs) are widely used by the man to manage crops and household insects. Here we used the cockroach, Nauphoeta cinerea, as an alternative model to study the effect of chlorpyrifos (CPF) on the acetylcholinesterase (AChE) and its reactivation by pralidoxime (2-PAM). The main objective was to determine the suitability of N. cinerea as a high-throughput animal model to study the behavioral and biochemical effects of CPF. Here, in silico approaches were also used to further refine the interaction of both CPF and 2-PAM with different sources of AChEs (human, mouse, fruit fly, and cockroach). Since data about the distribution of chemicals in N. cinerea are not available in the literature, we used methylene blue as an “indirect indicator” of CPF and 2-PAM distribution in cockroaches. After 40 min of administration, methylene blue was detected in the head region of cockroaches. A single injection of CPF (3.4 nmol in 10 µL) in the dorsal region of N. cinerea caused typical signs of OP poisoning (from 30 to 60 min after CPF injection). The administration of 2-PAM (10 min after the CPF) was able to reverse the behavioral and biochemical (AChE activity) changes induced by CPF. The in silico docking simulations between the cockroach AChE and the chemicals (CPF and 2-PAM) provided insight into the binding pose and molecular interactions of the chemicals with AChE structure. Thus, the N. cinerea can be a potential experimental model and reliable for researchers because the treatments with CPF and 2-PAM on this species had the same pattern as studies realized in the mammalian models.