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

Aluminum (Al), oxidative stress and impaired cholinergic functions have all been related to Alzheimer's disease (AD). The present study evaluates the effect of aluminum on acetylcholinesterase (AChE) and lipid peroxidation in the mouse brain. Mice were loaded by gavage with Al 0.1 mmol/kg/day 5 days per week during 12 weeks. The mice were divided into four groups: (1) control; (2) 10 mg/mL of citrate solution; (3) 0.1 mmol/kg of Al solution; (4) 0.1 mmol/kg of Al plus 10 mg/mL of citrate solution. AChE activity was determined in the hippocampus, striatum, cortex, hypothalamus and cerebellum and lipid peroxidation was determined in the hippocampus, striatum and cortex. An increase of AChE activity was observed in the fourth group (Al + Ci) in the hippocampus (36%), striatum (54%), cortex (44%) and hypothalamus (22%) (p<0.01). The third group (Al) presented a decrease of AChE activity in the hypothalamus (20%) and an enhancement in the striatum (27%). Lipid peroxidation, measured by TBARS (thiobarbituric acid reactive substances), was elevated in the hippocampus and cerebral cortex when compared with the control (p < 0.01). The effect of aluminum on AChE activity may be due to a direct neurotoxic effect of the metal or perhaps a disarrangement of the plasmatic membrane caused by increased lipid peroxidation.

NTPDase and 5'-nucleotidase activities in rats with alloxan-induced diabetes.

Diabetes is associated with a hypercoagulable state. In this study, we investigated the potential effects of alloxan-induced diabetes on the activities of the enzymes NTPDase (E.C. 3.6.1.5, apyrase, ATP diphosphohydrolase, ecto/CD39) and 5'-nucleotidase (E.C. 3.1.3.5, CD73) that can control the levels of ADP and adenosine, two substances that regulates platelet aggregation. In the alloxan-treated rats, NTPDase activity was significantly increased by 88 and 35% with ATP as substrate and by 156 and 58% with ADP as substrate in platelets and synaptosomes, respectively (P< 0.05). AMP hydrolysis was increased by 142% (platelets) and 70% (synaptosomes) in diabetic rats compared to control. These results demonstrate that alloxan-induced diabetes interferes with ATP, ADP, and AMP hydrolysis in platelets and synaptosomes. Taken together, these results may indicate that in diabetic rats both NTPDase and 5'-nuleotidase from the central nervous system (CNS) and platelets respond similarly with increased activity. Thus, we speculate that platelets could be used as a potential peripheral marker of central alterations in NTPDase and 5'-nucleotidase activities in diabetes.