Dias Glaecir R Mundstock, Schetinger Maria Rosa Chitolina, Spanevello Roselia, Mazzanti Cinthia Melazzo, Schmatz Roberta, Loro Vânia Lúcia, Morsch Vera Maria
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
Arch Toxicol. 2009 Mar;83(3):263-9. doi: 10.1007/s00204-008-0395-6. Epub 2008 Dec 17.
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.
本研究的目的是验证乙醇对血小板NTPD酶和5'-核苷酸酶活性的急性和慢性影响。这些酶通过调节腺嘌呤核苷酸的生物利用度和腺苷生成来调节血小板功能。在急性治疗中,通过胃管给予0.8、2.0、4.0、6.0和8.0 g/kg剂量的乙醇,对ATP、ADP和AMP的血小板水解产生双相或兴奋效应。以ATP为底物时,0.8和2.0 g/kg剂量的乙醇可使NTPD酶活性增加(分别增加44%和35%,P<0.0001),而以ADP为底物时,NTPD酶活性仅呈增加趋势。与对照组相比,4.0、6.0和8.0 g/kg乙醇可使ATP和ADP水解降低31%-77%(P<0.0001)。0.8和2.0 g/kg乙醇剂量下AMP水解呈增加趋势,但在较高剂量下被抑制45%-100%(P<0.0001)。慢性治疗包括在31周内口服20%乙醇溶液作为唯一液体来源,分别以ATP和ADP为底物时可抑制NTPD酶活性(分别降低15%和20%,P<0.05)。然而,5'-核苷酸酶介导的AMP水解增加了40%(P<0.05)。因此,我们推测乙醇对NTPD酶和5'-核苷酸酶活性的影响可能与酒精使用者中常见的血小板改变有关