Density functional method with continuum solvation model is used for calculation of partition coefficient logKOW and determination of lipophilicity of 22 most frequently used organophosphate type pesticides. Excellent agreement with experimental data is obtained using three different density functional approximations (one local, one general gradient and one hybrid), and our result highlights DFT as a reliable and trustworthy method for calculation and of lipophilicity for this important class of molecules. Furthermore, calculated lipophilicity results are associated with experimentally determined LD50 and LC50 values, showing that the most toxic pesticides are these with transient characteristics (medium lipophilicity), although this concussion must be taken with a caution due to the many factors influencing the ingestion and action of a certain substance in the body beside lipophilicity.

Diazinon (DZN) is an organophosphate insecticide which exerts its effect through the inhibition of acetylcholinesterase enzyme (AChE). In this work, we studied the development of tolerance to subchronic p.o. administration of DZN in rats, under both in vivo and in vitro conditions. A group of 20 rats (2 groups, n = 10) was administered p.o. the 1/10 of established LD50 DZN (namely 55.87 mg/kg bw) for 28 days. On the 14th and 28th day of study with isolated diaphragm and ileum, we examined the downregulation of nicotinic and muscarinic receptor function through Electrical Field Stimulation (EFS). Maximum contractility of the diaphragm was recorded on the 14th day of the study (25% higher compared to the non-treated rats), while on the 28th day the contractions almost did not differ from the values found in non-treated rats. EFS of isolated ileum on the 14th day of study caused significantly higher contractions compared to the non-treated rats, but after 28 days, ileum contractions decreased approximately to the level of contractions in non-treated rats. On the 14th study day, we also recorded increased amplitude of spontaneous ileum contractions, compared to non-treated rats. The application of increasing ACh concentrations caused dose-dependent ileum contractions, without statistically significant differences of median effective concentration (EC50) values in non-treated and treated rats. Tolerance to subchronic DZN administration develops due to various adaptation mechanisms, including the most important one-downregulation of nicotinic and muscarinic receptor function.

Deep proteomic analyses identified, in total, 159 master proteins (with 1% FDR and 2 unique peptides) from 26 protein families in the venom of Vipera ammodytes ammodytes (Vaa). Data are available via ProteomeXchange with the identifier PXD056495. The relative abundance of PLA2s is 11.60% of the crude venom, of which 4.35% are neurotoxic Ammodytoxins (Atxs). The neurotoxicity of the venom of Vaa and the neutralizing effect of the antivenom were tested on the neuromuscular preparation of the diaphragm (NPD) of rats. The activity of PLA2 in the venom of Vaa and its neutralization by the antivenom were determined under in vitro conditions. The Vaa venom leads to a progressive decrease in NPD contractions. We administered pre-incubated venom/antivenom mixtures at various ratios of 1:2, 1:10 and 1:20 (w/w) and observed the effects of these mixtures on NPD contractions. The results show that the mean effective time (ET₅₀) for NPD contractions with the 1:20 mixture is highly significantly different (p < 0.001) from the ET₅₀ for the venom and the ET₅₀ for the 1:2 and 1:10 mixture ratios. We also found a highly significant (p < 0.001) reduction in Na⁺/K⁺-ATPase activity in the NPD under the influence of the venom. The reduction in the activity of this enzyme was reversible by the antivenom. Under in vitro conditions, we have achieved the complete neutralization of PLA2 by the antivenom. In conclusion, the antivenom abolished the venom-induced progressive decrease in NPD contractions in a concentration-dependent manner. Antivenom with approximately the same mass proportion almost completely restores Na⁺/K⁺-ATPase activity in the NPD and completely neutralizes the PLA2 activity of the venom in vitro.

Background/Aim. Organophosphate pesticides (OPs) are used extensively worldwide in agriculture and forestry, and their application represents a major health problem for humans and animals. The aim of this study was to investigate the possibility of the adaptation of an organism to the pro-longed administration of a low dose of diazinon. Methods. The study was conducted on a total of 60 male Wistar rats. The first 30 rats were divided into four equal diazinon groups (n = 6) and the control one (corn oil). Diazinon was orally administered once at doses: 200, 400, 600, 800 mg/kg (one dose ? one group). The concentration of glucose, the activity of ?-amylase and the relative activity of LDH1-LDH5 isoenzymes in the blood were measured 24 hours after the application. The remaining 30 rats were divided into two equal diazinon groups (n = 10) and the control one (corn oil). The first group was treated during 7 days, and the second during 14 days with 55 mg/kg of diazinon (1/10 of previously determined LD50 value). The histopathology of the pancreas and the liver, as well as the relative activities of LDH isoenzymes in the blood, were determined after the completion of both time periods. Results. Single administration of increasing doses of diazinon resulted in a significant increase in the concentrations of glucose, activity of ?-amylase and LDH isoenzymes. Subacute application of a low diazinon dose induced histopathological changes in the pancreas manifested by acinar cell necrosis, and in the liver in the form of portal hepatitis and multifocal necrosis. The cumulative doses resulted in statistically significantly lower activities of LDH isoenzymes compared with the single administration of these doses, indicating a lower degree of the cells damage after the subacute diazinon administration. Conclusion. Subacute administration of a low dose of diazinon leads to a different adaptation degree of organs and organ systems to toxic effects caused by this organophosphate.