Acetylcholinesterase protective effects

Acetylcholinesterase was immobilised by entrapment into a PVA-SbQ matrix (see experimental details in Refs. [88,95]). The need of polymer hydration slightly increases the response times, when compared to other immobilisation techniques. Nevertheless, the entrapment presents the advantage of providing biosensors with longer lifetimes due to the protective effect of the polymer matrix. 

Compounds that affect activities of hepatic microsomal enzymes can antagonize the effects of methyl parathion, presumably by decreasing metabolism of methyl parathion to methyl paraoxon or enhancing degradation to relatively nontoxic metabolites. For example, pretreatment with phenobarbital protected rats from methyl parathion s cholinergic effects (Murphy 1980) and reduced inhibition of acetylcholinesterase activity in the rat brain (Tvede et al. 1989). Phenobarbital pretreatment prevented lethality from methyl parathion in mice compared to saline-pretreated controls (Sultatos 1987). Pretreatment of rats with two other pesticides, chlordecone or mirex, also reduced inhibition of brain acetylcholinesterase activity in rats dosed with methyl parathion (2.5 mg/kg intraperitoneally), while pretreatment with the herbicide linuron decreased acetylcholine brain levels below those found with methyl parathion treatment alone (Tvede et al. 1989). 

Schaumann OO found that pretreatment of mice with 2-PAM 1 reduced inhibition of acetylcholinesterase in brain by paraoxon much more effectively than those by DFP and 217-A0. The finding of some protection against all three OP compounds could depend on direct reaction between the last two inhibitors and the oxime, with a reduction in inhibition of the enzyme. A similar consideration applies to the report by Bisa et al. that IV protected serum and brain cholinesterase from inhibition by paraoxon administered later at twice the LD5O. Although the same intraperitoneal dose of IV (7 mg) was found to protect the cholinesterase of rat serum and brain only incompletely from inhibition by DFP at 5 times the LD50, that of serum recovered its normal activity by 20 h after the dose of DFP, whereas that of brain required 26 h for recovery. 

Manzamines A, E, F, and Y, 8-hydroxymanzamine A and neo-kauluamine did not show any effect on acetylcholinesterase (AChE) or a-amyloid cleaving enzyme (a-secretase, BACEl) using invitro enzymatic assays. Likewise these compounds did not exhibit any significant ability to protect human neuroblastoma SH-SY5Ycells against oxidative stress-induced cell death [44]. 

Exposure to some organophosphate cholinesterase inhibitors results in a delayed neuropathy characterized by degeneration of axons and myelin. This effect is not associated with the inhibition of acetylcholinesterase, but rather with the inhibition of an enzyme described as neuropathy target esterase (NTE) however, the exact mechanism of toxicity is not yet fully understood (Munro et al., 1994). For some organophosphate compounds, delayed neuropathy can be induced in experimental animals at relatively low exposure levels, whereas for others the effect is only seen following exposure to supralethal doses when the animal is protected from the acute toxic effects caused by cholinesterase inhibition. 

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