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The article discusses a study that examined the cholinergic and non-cholinergic targets of organophosphorus pesticides (OP).

In efficacy testing of experimental oximes, traditionally reactivation of OP-inhibited acethylcholinesterase (AChE) has been analysed by comparing the obtained effects of the single dose with the control [1]. However, quantitative analysis of in vivo dose-response data by benchmark dose (BMD) approach would improve both identification and quantification of the effect and it will allow more rigorous comparison of different oximes efficacies [2]. Thus, we have evaluated in vivo dose-response relationship for two promising experimental oximes, K203 and K027, concerning reactivation of diaphragmal AChE inhibited by dichlorvos (DDVP). To compare the oximes effects, BMD-covariate method was used to estimate oxime dose (with 90% confidence intervals) that elicits a pre-specified effect size of 50% (1.5-fold increase in AChE activity compared to DDVP-treated group). Wistar rats (5/group) were treated with oxime (0/1.25/2.5/5/25/50% LD50 im) immediately after DDVP challenge (75% LD50 sc). Activity of AChE was measured in rat diaphragm homogenates by modified Ellman's method 60 min after the treatment. Dose-response modeling was done by PROAST software (version 65.5, RIVM, Nederlands). Exponential model m5-ab (y=a[c-(c-1)exp(-bxd)]) was selected as best estimate with parameters: aK203=0.1525, aK027=0.1498, bK203=0.008472, bK027=0.03941, c=2.117 and d=0.8916. Derived BMD50 were K203=117 (56, 209) and K027=21 (10, 37) µmol/kg bw, indicating that oxime K027 induces the same effect size with 5.5-times lower dose compared to oxime K203. Moreover, obtained confidence intervals of BMDs did not overlap allowing the conclusion that more potent dose-response relationship belongs to experimental oxime K027. [ABSTRACT FROM AUTHOR]

Introduction: Contact herbicide diquat (DQ), redox cycling compound, mediates its systemic toxicity throughout the enlarged production of free radicals. Target organs are liver and kidney in humans. To-date, the mechanism of DQ-induced neurotoxicity has not been rationalized., Objective: The objectives of the study were to examine the ability of DQ to induce oxidative stress (OS) and/or nitrosative stress (NS) upon intrastriatal (i.s.) administration and to investigate the role of nitric oxide (NO(x)) using NG-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of nitric oxide synthase (NOS) in the pretreatment of DQ i.s. administration., Material and Methods: The experiment was conducted on Wistar rats, randomly divided in experimental groups, receiving different treatments i.s. applied. Parameters of OS/NS such as: superoxide anion radical (O(2)(•-)), superoxide dismutase (SOD), malondialdehyde (MDA) and nitrates (NO(3)(-)) were measured in the cortex (bilaterally), at 30(th) min, 24 hours and 7 days after the treatments., Results: Lethargy and high mortality rate were observed only in the DQ group (within 24 hours and 2-3 hours, respectively) after awakening from anesthesia. Markedly increased production of NO(x) and O(2)(•-) along with elevated lipid peroxidation altogether contributed to DQ neurotoxicity. The most importantly, the L-NAME i.s. pretreatment protected treated animals from dying and diminished OS/NS response against DQ-induced neurotoxicity., Conclusion: The i.s. pretreatment with L-NAME resulted in neuroprotection against DQ neurotoxity, based on animal survival and reduced LPO in the cortex.