Evaluation of the effects of aluminium, ethanol and their combination on rat brain synaptosomal integral proteins in vitro and after 90-day oral exposure.
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Kohila T, Parkkonen E, Tahti H
Evaluation of the effects of aluminium, ethanol and their combination on rat brain synaptosomal integral proteins in vitro and after 90-day oral exposure.
Arch Toxicol. 2004 May;78(5):276-82.
- PubMed ID
- 15254985 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Aluminium Sodium/potassium-transporting ATPase subunit alpha-1 Protein Humans UnknownBinderDetails Aluminium phosphate Sodium/potassium-transporting ATPase subunit alpha-1 Protein Humans UnknownNot Available Details Aluminum acetate Sodium/potassium-transporting ATPase subunit alpha-1 Protein Humans UnknownNot Available Details