Reactions of Acetylcholinesterase with Organophosphorus Insecticides

The study characterized the reaction types of acetylcholinesterase (AChE) with different pesticides and suggested immediate medical treatments for poisoning cases. We retrospectively investigated the medical records of 120 poisoned cases. AChE activities were categorized into 3 groups. Extreme inhibition (EI), (307-769 u/L), severe inhibition (SI) (770-2888 u/L) Moderate inhibition (MI) (3000-4999 u/L), and less inhibition (LI) (5000-7000 u/L). These data were associated with occupational pesticides exposure to organophosphorus insecticides (OPI), carbamate insecticide (CI) s and general pesticides (GP). Medical treatments showed that class of EI did not show any cure signs with atropine administration whereas other classes (SI, MI and LI) showed positive responses with atropine administration. Class of EI showed positive sings with Toxogonin administration after several dose. These data suggested AChE in EI class has a strong affinity to bound with OP forming irreversible and/or stable complex, whereas in CI and GP, AChE has low affinity and form reversible non-stable complexes. It can be concluded that Toxogonin can be given to EI cases of AChE activity level as successful and immediate medical treatment for OP poisoning cases. On the other case atropine is the best antidote. IOINTRODUCTION AChE is an important enzyme in the nervous system. It catalyzes the hydrolysis of the neurotransmitter acetylcholine (ACh) in the synaptic gaps. This enzyme is sensitive to react with many inhibitors such as organophosphorus insecticides and carbamate compounds. Its reactions with inhibitors may be associated with Ach accumulation in the synaptic gaps resulting in the appearance of cholinergic symptoms. This is in agreement with previous reports [1-5]. So far reactions of AChE with OPI have been reported [6], the author revealed several mechanisms. So far, AChE is sensitive to a wide number of pesticides and other chemical compounds and can be inhibited by them. The magnitude of inhibition is different from molecule to another [7-9]. The above mentioned studies were limited to toxicity or inhibition studies. Types of possible AChE reactions with OPs or pesticides in general was not investigated or remains in the primary stages. This investigation is concerned with the reaction types of AChE with organophosphorus and carbamate pesticides, with emphasis on electronegativity of atoms on the molecular structure MATERIALS AND METHODS Data Collection About 120 medical reports of those medically visited the hospital for occupational pesticide treatments such as accidental poisoning, vomiting, diarrhea and headache during work were collected and analyzed. The medical file included results of acetylcholine esterase activity (AChE) measurement. Additionally, the medical files contained data of pesticides used during the medical treatment and the antidotes used for medical treatments. Statistical Analysis The collected data were analyzed using an Excel program. The pesticides used were arranged into different groups such as OPI, CI, and GP. AChE activity was subdivided into four groups as follows: group 1 (EI) [307-769 u/L], group 2 (SI) [770-2888 u/L, group 3 (MI) [3000-4982 u/L] group 4 (LI) [5000-7000 u/L] and normal range [7001-9776 u/L]. The pesticides found were listed in Groups. RESULTS Levels of AChE Levels of AChE detected in blood serum of farmers occupationally exposed to different pesticides are shown in Table 1 Proposed reactions of AChE with different pesticides Pesticides in general can react with AChE in four different Central Bringing Excellence in Open Access   El-Nahhal Y (2018) Email: J Pharmacol Clin Toxicol 6(2): 1108 (2018) 2/4 ways: 1. Strong ionic interaction between the anionic site on the AChE and the cationic Phosphonium ion in OP insecticides 2. Weak ionic interaction between the anionic site on the AChE and the cationic Phosphonium ion in OP 3. Hydrogen bonding between the hydrogen atoms of the AChE and O-atom in the OP 4. Hydrophobic/hydrophobic interaction between the hydrogen atoms in OP molecules and hydrogen atoms in esteratic site on the enzyme surfaces. Schematic diagram of these reactions are shown in Figure 1. Medical treatments The cases of AChE levels visited the main hospital in Gaza listed in Table 1 were treated with both atropine and Toxogonin, the EI cases and SI cases were treated with atropine but without significant progress. Then were give Toxogonin, few days later the level of AChE increased indication progress in the medical treatments. On the other hands MI and LI cases show tremendous medical progress from the first dose indication of weak interaction between pesticide and AChE. DISCUSSION The data presented in Table 1 shows the inhibition levels of AChE and the number of cases. The presented results clearly show extreme and severe inhibition levels among farmers. These levels are related to the high toxicity of applied pesticides found in the medical records of the farmers. These results are in accordance with recent levels [5,10]. Furthermore, the data in Table 2 clearly show the chemical structure, number of electron with drawing atoms or groups and the LD50. It is obvious that the OP compounds containing aromatic and aliphatic groups. It can be noticed that LD50 value decreased (higher toxicity) as the OP compound contained electron withdrawing atoms or groups more that2. The highest toxicity was found with fenamiphos, which has four electron with drawing groups whereas the lowest toxicity was found with Glyphosate, which has the lowest number of electron with drawing groups, only one group. These observation indicate the importance of electron withdrawing groups that attached to the phosphorus atom in the OP molecules. The explanation of these results is that electron with drawing group can create partial positive change on the phosphorus atom. As the number of electron with drawing groups increased in the OP molecules as in fenamiphos molecules, the potential formation of positive charge on the phosphorus atom increased leading to a possible formation of a phosphonium ion which can strongly react with AChE forming irreversible complexes as in the EI cases and SI (Table 1). Furthermore, the degree of positive charges creation on the phosphorus atom, the degree of strength interaction between the OP molecules and AChE. These reactions are proposed in Figure 1. It can be noticed that four reaction categories are proposed based on the degree of electronegativity of the attached groups with phosphorus. So far at highest electronegativity, the Figure 1 The possible reactions of AChE with Ops. Central Bringing Excellence in Open Access   El-Nahhal Y (2018) Email: J Pharmacol Clin Toxicol 6(2): 1108 (2018) 3/4 Table 1: levels of AChE among farmers exposed to different pesticides during work. Type of inhibition AChE levels No cases % Pesticides found LD50-range mg/kg EI 307-769 u/l 15 12.82 OP insecticides 6-27 SI 770-2888 u/l 16 13.68 Carbamate insecticides 8-30 MI 3000-4982 u/l 10 8.55 OP Pesticides 1375 LI 5000-7000 u/l 30 25.64 All pesticides >1500 Normal range 7001-9776 u/l 46 39.31 Control group 00 The name and chemical structure of pesticides found in EI and SI groups are shown in Table 2 Table 2: Name, chemical structures, electron withdrawing groups, and LD50. Name Chemical structure (electron withdrawing groups) *LD50 mg/kg Azinophos-methyl 3 12