, 2010). Our study demonstrated PF-02341066 manufacturer that the Na+/K+-ATPase activity was not modified by IBTC at any of the concentrations tested, indicating that IBTC

has no toxic properties to neurons. Previous reports have demonstrated the importance of thiol groups for Na+/K+-ATPase catalysis and –SH groups of this enzyme are highly susceptible to oxidizing agents (Bavaresco et al., 2003 and de Assis et al., 2003). The unchanged NPSH levels found here are in agreement with the unchanged activities of ALA-D and Na+/K+-ATPase. We also demonstrate that IBTC did not alter the activity of AChE and BChE, enzymes related to dysfunctions in the cholinergic selleck products neurotransmission (Mukherjee et al., 2007) and

to systemic inflammatory conditions, such as diabetes mellitus, hypertension, insulin resistance, and hyperlipidemia (Das, 2007). AChE and BChE are strongly related to the intoxications caused by pesticides and the implications of pesticides residues on human health have yet to be comprehensively documented. Pesticides may induce oxidative stress, leading to generation of free radicals and alterations in antioxidants, oxygen free radicals, scavenging enzyme systems, and lipid peroxidation. This way, after verifying that IBTC does not alter antioxidant systems and has no toxic effects, we tested the capacity of IBTC to protect and reactivate the activity of AChE and BChE after inhibition

with MAP. In human erythrocyte ghost and in human plasma BChE, IBTC was able to protect and reactivate both enzymes from MAP inhibition at all concentrations tested (Fig. 5 and Fig. 6). The protective activity for AChE and BChE against MAP inhibition works via competitive inhibition. Molecular docking results indicate that IBTC can enter the active site of AChE by binding to the peripheral anionic site (Trp134 and Tyr124) and Lepirudin internal anionic site (Thr83 and Tyr337), thus preventing MAP from accessing the catalytic residue Ser203 and protecting AChE and BChE from inhibition, and proving that IBTC cannot itself inhibit AChE or BChE, since in vitro tests demonstrate that the presence of IBTC on these sites do not affect AChE and BChE activities. Our most interesting result is that IBTC can reactivate AChE and BChE after inhibition by MAP. As far as we know, there are few compounds that are not oximes that can reactivate AChE and BChE inhibited by OPs and there is no literature concerning the use of thiosemicarbazones against OP intoxication. In that way, our study demonstrates for the first time that a thiosemicarbazone derivate can protect and reactivate AChE and BChE from OP inhibition.