Very little is known about the effects of chronic exposure to relatively low levels of anticholinesterase insecticides or how the effects of chronic exposure compare to those of higher, intermittent exposure. To that end, adult male rats were fed an anticholinesterase insecticide, chlorpyrifos (CPF), for 1 year at three levels of dietary exposure: 0, 1, or 5 mg/kg/day (0+oil, 1+oil, and 5+oil). In addition, half of each of these groups also received a bolus dosage of CPF in corn oil ("spiked" animals; 60 mg/kg initially and 45 mg/kg thereafter) every 2 months (0+CPF, 1+CPF, 5+CPF). Animals were analyzed after 6 or 12 months of dosing, and again 3 months after cessation of dosing (i.e., "recovery" animals-six experimental groups with n = 4-6/group/time point). Cholinesterase (ChE) activity was measured in retina, whole blood, plasma, red blood cells, diaphragm, and brain [pons, striatum, and the rest of the brain (referred to simply as "brain")]. Muscarinic receptor density was assessed in retina, pons, and brain, whereas dopamine transporter density and the levels of dopamine and its metabolites were assessed in striatum. Cholinesterase activity at 6 and 12 months was not different in any of the tissues, indicating that a steady state had been reached prior to 6 months. The 1+oil group animals showed ChE inhibition only in the blood, whereas the 5+oil group exhibited > or = 50% ChE inhibition in all tissues tested. One day after the bolus dose, all three groups (0+CPF, 1+CPF, 5+CPF) showed > or = 70% ChE inhibition in all tissues. Muscarinic receptor density decreased only in the brain of the 5+oil and 5+CPF groups, whereas dopamine transporter density increased only at 6 months in all three spiked groups. Striatal dopamine or dopamine metabolite levels did not change at any time. Three months after CPF dosing ended, all end points had returned to control levels. These data indicate that, although chronic feeding with or without intermittent spiked dosages with CPF produces substantial biochemical changes in a dose- and tissue-related manner, there are no persistent biochemical changes.
Differences were observed in the extent of thermal inactivation of human butyrylcholinesterase (BuChE) and eel acetylcholinesterase (AChE). BuChE was more resistant to 57 degrees C inactivation than was AChE. Thermal inactivation of BuChE was reversible and followed first-order kinetics. AChE thermal inactivation was irreversible and did not follow first-order kinetics. AChE was marginally protected from thermal inactivation by the "nonspecific salts" ammonium sulfate and sodium chloride and to a greater extent by the "active site-specific salts" choline chloride, sodium acetate, and acetylcholine iodide. This protection was accompanied by a loss of absorbance at 280 nm. This data supports the hypothesis that thermal inactivation of AChE occurs by conformational scrambling and that aromatic amino acid residue(s) are involved in this process.
Cuticle tissue homogenates (CTHs) from Callinectes sapidus premolt cuticle bound approximately 367% more Ca2+ ions than did those from the postmolt cuticle. The pH-stat assay which was used to compare in vitro CaCO3 nucleation times confirmed that the premolt CTHs had greater inhibitory activity than did the postmolt CTHs. This inhibitory activity was indicated by CaCO3 nucleation times in excess of control values. Premolt nucleation times exceeded those of postmolt samples by approximately 340%. A positive correlation was observed between Ca2+ binding and calcification inhibitory activity for both premolt and postmolt CTHs. Heat pretreatment of CTHs at 70 degrees C for a 24-hr period had no significant effect on their Ca2+ binding. However, this heat pretreatment decreased their calcification inhibitory activity. Pretreatment of CTHs with Ca2+ diminished their calcification inhibitory activity. These results are consistent with a mechanism for inhibition of biocalcification by these proteins which involves their initial reversible binding to nascent calcite nuclei growth steps and kinks, rather than their in vivo interaction with free Ca2+ ions in solution.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.