Evaluation of the effects of aluminium, ethanol and their combination on rat brain synaptosomal integral proteins in vitro and after 90-day oral exposure

Abstract

The effects of aluminium lactate (Al-lactate) on the rat cerebral synaptosome integral proteins adenosinetriphosphatase (ATPase) and acetylcholinesterase(AChE) were studied in vitro and in vivo. Coexposure with ethanol (EtOH) was studied in both situations. Isolation of synaptosomes was carried out using isoosmotic Percoll gradients. In in vitro experiments, the synaptosomes were exposed to different concentrations of Al-lactate in the incubation mixture. Al-lactate caused decreases in total ATPase and AChE activities concentration dependently. The decrease in ATP activity started at 0.2 mM concentration, and concentration for the 50% decrease of the enzyme activity (EC50 ) was 1.1 mM. The decrease in AChE activity started at 5-10 mM concentration, and the EC50 value was 15.8 mM. Coexposure with ethanol (2 mM) increased the EC50 values similarly in both cases. After 90-day oral exposure of rats to Al-lactate (91.8 mg/kg/day), the serum aluminium level was 0.9-1.3 ptM/l. Coexposure with EtOH(3.0 g/kg/day) did not significantly increase the blood Al(0.7 2.2 pM/l). Aluminium exposure caused a decrease in the blood EtOH concentration (0.6 mM/1) compared with blood EtOH (12.3 mM/1) in the rats exposed to ethanol only. In the rats studied 2 weeks after the Al exposure, the activities of ATPase and AChE were significantly lower than in the rats studied immediately after the exposure. Correspondingly, a significant decrease in AChE activity was found in Al and EtOH-exposed rats, but in the control rats there were no differences between the study groups. Immediately after the 90-day dosing, the exposed rats did not differ significantly from the control rats. Based on the in vitro results, the neural membrane integral proteins ATPase and AChE may be considered as targets for the effects of aluminium and ethanol. Ninety-day in vivo exposure of rats to aluminium caused decrease in ATPase and AChE activities, detectable 2 weeks after the exposure.

Does neurotransmission impairment accompany aluminium neurotoxicity?

“…This assumption is also supported by the biphasic effects of aluminium on enzyme activity [206,213], ionic strength dependence of the inhibitory effect [226] and dissimilarity of IC 50 values found (i.e. [211,220]), when different exposure protocols and biological preparations were used. After acetylcholine hydrolysis, choline is taken up by presynaptic nerve terminals.…”

“…The effect of aluminium on acetylcholinesterase has been studied either in vivo or in vitro (i.e. [114,116,120,123,125,145,158,[206][207][208][209][210][211][212][213][214][215][216][217][218][219][220][221][222][223]), and both, stimulatory and inhibitory, effects have been reported.…”

Acetylcholinesterase activation and enhanced lipid peroxidation after long-term exposure to low levels of aluminum on different mouse brain regions

“…The dose utilized in this study (0.1 mmol Al/kg) was considered low when compared with other studies using oral Al administration [14][15][16][24][25][26]. Citrate was used because it increases Al absorption [27,28], probably by enhancing Al solubility [22].…”

“…3.1.1.7) activity have been described in a large number of studies [4,[6][7][8][9][10][11][12][13][14][15][16][17], yet results are contro- versial and both activation and inhibition of AChE activity have been reported. In fact, these controversies could be explained by the different methods and doses of Al administration, differences in the biological samples assayed, differing periods of exposure (long-term and short-term) and by the metal speciation.…”

Decreased Beta2*‐nicotinic acetylcholine receptor availability after chronic ethanol exposure in nonhuman primates

“…One potential hypothesis is that during acute abstinence there are individual differences in endogenous ACh levels as a result of nAChR neuroadaptations to ethanol exposure. ACh is capable of interfering with [ 123 I]5-IA binding (Fujita et al, 2003) and alcohol consumption and withdrawal modulates endogenous ACh and cholinergic function (Arendt et al, 1989; Kohila et al, 2004; Nestby et al, 1997). Thus, changes in changes in β 2 *-nAChR availability during acute alcohol withdrawal may reflect alterations in receptor number combined with changes in the levels of occupancy of these receptors by ACh.…”