Effects of Organophosphorus and Pyrethroid Pesticides on Antioxidant Enzymes and Reactivation Effects of Pralidoxime: In vitro Studies

The present study was aimed to assess the inhibition effects of organophosphate pesticides, malathionR, dichlorvosR; pyrethroid pesticides, deltamethrinR, λ-cyhalothrinR on antioxidantenzymes and reactivation ability of pralidoxime against pesticide inhibited-antioxidant enzymes. Oximes were reported by reactivation ability against organophosphate inhibited- acetylcholinesterase and we focused to investigate the reactivation effect of pralidoxime against organophosphate inhibited–antioxidant enzymes. IC50 values were determined by means of activity percentage diagrams. The concentrations of deltamethrinR, malathionR,dichlorvosR, λ-cyhalothrinR that inhibited 50% of catalase were 5.2 μM, 158 μM, 133 μM,320 μM, respectively, inhibited 50% of superoxide dismutase were 62 μM, 240 μM, 328 μM, 2320 μM, respectively and inhibited 50% of glutathione peroxidase were 0.7 μM, 1198 μM, 1638 μM, 98 μM, respectively. All pesticide doses showed inhibition effect on antioxidant enzymes. DeltamethrinR was found to be a more potent inhibitor for the antioxidant enzymesfollowed by the rest of pesticides used in this study. Reactivation effect of pralidoxime was determined for organophosphate inhibited-enzymes. Reactivation results showed that only catalase is reactivated by pralidoxime against dichlorvosR and malathionR. Under the exposureof 50-800 μM malathionR concentrations, catalase activity % was calculated as 72-11%,respectively. After inhibited catalase by malathionR incubated with 1 mM and 10 mMpralidoxime, catalase activity % was calculated as 92-31% and 98-39%, respectively. Under the exposure of 100-1500 μM dichlorvosR concentrations, catalase activity % was calculatedas 50-6%, respectively. After inhibited catalase by dichlorvosR incubated with 1 mM and 10mM pralidoxime, catalase activity % was calculated as 95-30% and 93-28%, respectively. When the results are examined, it is seen that increasing the pralidoxime concentration does not significantly affect the reactivation percentage of the catalase enzyme.

Empirical validation of directed functional connectivity

Mapping directions of influence in the human brain connectome represents the next phase in understanding its functional architecture. However, a host of methodological uncertainties have impeded the application of directed connectivity methods, which have primarily been validated via 'ground truth' connectivity patterns embedded in simulated functional MRI (fMRI) and magneto-/electro-encephalography (MEG/EEG) datasets. Such simulations rely on many generative assumptions, and we hence utilized a different strategy involving empirical data in which a ground truth directed connectivity pattern could be anticipated with confidence. Specifically, we exploited the established 'sensory reactivation' effect in episodic memory, in which retrieval of sensory information reactivates regions involved in perceiving that sensory modality. Subjects performed a paired associate task in separate fMRI and MEG sessions, in which a ground truth reversal in directed connectivity between auditory and visual sensory regions was instantiated across task conditions. This directed connectivity reversal was successfully recovered across different algorithms, including Granger causality and Bayes network (IMAGES) approaches, and across fMRI ('raw' and deconvolved) and source-modeled MEG. These results extend simulation studies of directed connectivity, and offer practical guidelines for the use of such methods in clarifying causal mechanisms of neural processing.