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1.
Cell Mol Neurobiol ; 37(1): 53-63, 2017 Jan.
Article in English | MEDLINE | ID: mdl-26879755

ABSTRACT

Thyroid hormones have an influence on the functioning of the central nervous system. Furthermore, the cholinergic and purinergic systems also are extensively involved in brain function. In this context, quercetin is a polyphenol with antioxidant and neuroprotective properties. This study investigated the effects of (MMI)-induced hypothyroidism on the NTPDase, 5'-nucleotidase, adenosine deaminase (ADA), and acetylcholinesterase (AChE) activities in synaptosomes of rats and whether the quercetin can prevent it. MMI at a concentration of 20 mg/100 mL was administered for 90 days in the drinking water. The animals were divided into six groups: control/water (CT/W), control/quercetin 10 mg/kg, control/quercetin 25 mg/kg, methimazole/water (MMI/W), methimazole/quercetin 10 mg/kg (MMI/Q10), and methimazole/quercetin 25 mg/kg (MMI/Q25). On the 30th day, hormonal dosing was performed to confirm hypothyroidism, and the animals were subsequently treated with 10 or 25 mg/kg quercetin for 60 days. NTPDase activity was not altered in the MMI/W group. However, treatment with quercetin decreased ATP and ADP hydrolysis in the MMI/Q10 and MMI/Q25 groups. 5'-nucleotidase activity increased in the MMI/W group, but treatments with 10 or 25 mg/kg quercetin decreased 5'-nucleotidase activity. ADA activity decreased in the CT/25 and MMI/Q25 groups. Furthermore, AChE activity was reduced in all groups with hypothyroidism. In vitro tests also demonstrated that quercetin per se decreased NTPDase, 5'-nucleotidase, and AChE activities. This study demonstrated changes in the 5'-nucleotidase and AChE activities indicating that purinergic and cholinergic neurotransmission are altered in this condition. In addition, quercetin can alter these parameters and may be a promising natural compound with important neuroprotective actions in hypothyroidism.


Subject(s)
5'-Nucleotidase/metabolism , Acetylcholinesterase/metabolism , Hypothyroidism/enzymology , Nucleoside-Triphosphatase/metabolism , Quercetin/therapeutic use , Synaptosomes/enzymology , Animals , Enzyme Activation/drug effects , Enzyme Activation/physiology , Hypothyroidism/drug therapy , Male , Polyphenols/pharmacology , Polyphenols/therapeutic use , Quercetin/pharmacology , Rats , Rats, Wistar , Synaptosomes/drug effects
2.
Arch Toxicol ; 83(3): 263-9, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19089412

ABSTRACT

The objective of this study was to verify the acute and chronic effects of ethanol on platelet NTPDase and 5'-nucleotidase activities. These enzymes modulate platelet function by regulating adenine nucleotide bioavailability and adenosine production. In the acute treatment, doses of 0.8, 2.0, 4.0, 6.0 and 8.0 g/kg ethanol were administered via orogastric tube, and induced a biphasic or hormetic effect on ATP, ADP and AMP platelet hydrolysis. Ethanol at a dose of 0.8 and 2.0 g/kg increased NTPDase activity (44 and 35%, P < 0.0001) with ATP as substrate, whereas when ADP was used there was only a tendency for NTPDase activity to increase. ATP and ADP hydrolysis decreased by 31-77% (P < 0.0001) in 4.0, 6.0 and 8.0 g/kg of ethanol compared to the control. AMP hydrolysis showed a tendency to increase at ethanol doses of 0.8 and 2.0 g/kg, but was inhibited by 45-100% (P < 0.0001) at the higher doses. Chronic treatment consisted of the oral administration of 20% ethanol solution during 31 weeks as the only source of liquid and inhibited NTPDase activity (15 and 20%, P < 0.05) with ATP and ADP as substrate, respectively. However, AMP hydrolysis by 5'-nucleotidase increased by 40% (P < 0.05). Thus, we speculate that the effects of ethanol on NTPDase and 5'-nucleotidase activities could be related with the platelets alterations commonly observed in alcohol users.


Subject(s)
Adenine Nucleotides/metabolism , Blood Platelets/drug effects , Ethanol/toxicity , Toxicity Tests, Acute , Toxicity Tests, Chronic , 5'-Nucleotidase/analysis , 5'-Nucleotidase/antagonists & inhibitors , 5'-Nucleotidase/metabolism , Animals , Blood Platelets/enzymology , Blood Platelets/metabolism , Dose-Response Relationship, Drug , Hydrolysis/drug effects , Male , Rats , Rats, Wistar , Time Factors
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