The effect of aluminium on NTPDase and 5'-nucleotidase activities from rat synaptosomes and platelets.

Aluminium (Al), a neurotoxic compound, has been investigated in a large number of studies both in vivo and in vitro. In this study, we investigated the effect in vivo of long-term exposure to Al on NTPDase (nucleoside triphosphate diphosphohydrolase) and 5'-nucleotidase activities in the synaptosomes (obtained from the cerebral cortex and hippocampus) and platelets of rats. Here, we investigated a possible role of platelets as peripheral markers in rats. Rats were loaded by gavage with AlCl(3) 50 mg/(kg day), 5 days per week, totalizing 60 administrations. The animals were divided into four groups: (1) control (C), (2) 50 mg/kg of citrate solution (Ci), (3) 50 mg/kg of Al plus citrate (Al+Ci) solution and (4) 50 mg/kg of Al (Al). ATP hydrolysis was increased in the synaptosomes from the cerebral cortex by 42.9% for Al+Ci and 39.39% for Al, when compared to their respective control (p<0.05). ADP hydrolysis was increased by 13.15% for both Al and Al+Ci, and AMP hydrolysis increased by 32.7% for Al and 27.25% for Al+Ci (p<0.05). In hippocampal synaptosomes, the hydrolysis of ATP, ADP and AMP, was increased by 58.5%, 28.5% and 25.92%, respectively, for Al (p<0.05) and 36.7%, 22.5% and 37.64% for Al+Ci, both when compared to their respective controls. ATP, ADP and AMP hydrolysis, in platelets, was increased by 172.3%, 188.52% and 92.1%, respectively in Al+Ci, and 317.9%, 342.8% and 177.9%, respectively, for Al, when compared to their respective controls (p<0.05). Together, these results indicate that Al increases NTPDase and 5'-nucleotidase activities, in synaptosomal fractions and platelets. Thus, we suggest that platelets could be sensitive peripheral markers of Al toxicity of the central nervous system.

Enzymes that hydrolyze adenine nucleotides in chronic renal failure: relationship between hemostatic defects and renal failure severity.

The activities of the enzymes NTPDase (E.C.3.6.1.5, apyrase, ATP diphosphohydrolase, ecto-CD 39) and 5'-nucleotidase (E.C.3.1.3.5, CD 73) were analyzed in platelets from patients with chronic renal failure (CRF), both undergoing hemodialysis treatment (HD) and not undergoing hemodialysis (ND), as well as from a control group. The results showed an increase in platelet NTPDase activity in CRF patients on HD treatment (52.88%) with ATP as substrate (P<0.0001). ADP hydrolysis was decreased (33.68% and 39.75%) in HD and ND patients, respectively. In addition, 5'-nucleotidase activity was elevated in the HD (160%) and ND (81.49%) groups when compared to the control (P<0.0001). Significant correlation was found among ATP, ADP and AMP hydrolysis and plasma creatinine and urea levels (P<0.0001). Patients were compared statistically according the time of hemodialysis treatment. We found enhanced NTPDase and 5'-nucleotidase activities between 49 and 72 months on HD patients. Our result suggests the existence of alterations in nucleotide hydrolysis in platelets of CRF patients. Possibly, this altered nucleotide hydrolysis could contribute to hemostasis abnormalities found in CRF.

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.

Changes in acetylcholinesterase (AchE) activity in lymphocytes and whole blood in acute lymphoblastic leukemia patients.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a type of cancer that affects lymphocytes and it is the most common form of cancer in children. Acetylcholinesterase (AChE) is well known as having non-cholinergic functions and has been detected in the blood and plasma of humans including in lymphocytes. Thus, we investigated whole blood and lymphocyte AChE activity in patients with ALL. METHODS: This study was performed on 72 children with ALL divided into 4 groups: newly diagnosed, remission induction, remission maintenance and out-of-treatment and one control group of 50 healthy subjects. We determined AChE activity in whole blood and lymphocytes of these patients. RESULTS: Results demonstrated that whole blood AChE activity was enhanced in the newly diagnosed group and reduced in the remission induction and remission maintenance groups in relation to the control group. For lymphocyte AChE activity we found an increase in the newly diagnosed group and a decrease in the remission induction group in relation to the control. CONCLUSIONS: These results suggest that AChE activity was altered in ALL patients. This fact may be related with the essential role played by AChE in the development of hematological disease and its contribution to the regulation of immune function.

Diet-induced changes in AChE activity after long-term exposure.

In the present study we investigated a potential mechanism by which high sugar (HS) and high fat (HF) diets could affect acetylcholinesterase (AChE) activity. The treatment with HS and HF diet was done for six months on male and female rats. The results showed decreased hippocampal AChE activity in male and females receiving HS and HF diets (HS 24% and 36%; HF 38% and 32%, males and females, respectively; P < 0.05). The activity in the cerebral cortex was reduced in males (49 and 40%) and females (19 and 17%) (P < 0.05) on HS and HF diets, respectively. In the hypothalamus AChE activity was decreased on HS diet in males (46%) and female (25%) (P < 0.05) and also on HF diet in males (34%) and females (21%) (P < 0.05). However, in the cerebellum no changes in AChE activity were observed. These results indicate that HS and HF diets produced mainly inhibition in acetylcholine degradation. It probably indicates a chronic alteration induced by these diets on the cholinergic system.