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[过氧化氢酶激活剂和抑制剂对大鼠肝脏和大脑中乙醇药代动力学特征以及乙醇和醛代谢酶活性的影响]

[Effects of catalase activators and inhibitors on ethanol pharmacokinetic characteristics and ethanol and aldehyde-metabolizing enzyme activities in the rat liver and brain].

作者信息

Bardina L R, Pron'ko P S, Satanovskaia V I, Alieva E V

出版信息

Biomed Khim. 2010 Jul-Aug;56(4):499-505.

Abstract

The effects of catalase regulators (aminotriazole, lead acetate, taurine, di-2-ethylhexylphthalate) on the preference for ethanol, its pharmacokinetics, and activities of rat liver and brain ethanol and acetaldehyde-metabolizing enzymes were studied. Lead acetate (100 mg/kg, i.p., 7 days), aminotriazole (1 g/kg, i.p., 7 days), and taurine (650 mg/kg, i.g., 14 days) decreased ethanol consumption under conditions of free choice (10% ethanol water), whereas di-2-ethylhexylphthalate (300 mg/kg, i.g., 7 days) did not exert any effect on this parameter. Taurine, lead acetate and di-2-ethylhexylphthalate significantly activated liver ADH, MEOS and catalase peroxidase activity. Aminotriazole also activated ADH and MEOS, but inhibited liver catalase. The activities of liver and brain A1DH as well as catalase were insignificantly changed by this treatment. The 7-day administration of lead acetate, di-2-ethylhexylphthalate and aminotriazole administrations significantly influenced the ethanol (2 g/kg., i.p.) pharmacokinetic parameters: the area under the pharmacokinetic curve and the elimination half-life time were significantly reduced, whereas the elimination constant and clearance were increased. This unequivocally indicates accelerated ethanol elimination. The 14-day ingestion of taurine insignificantly changed the parameters of ethanol pharmacokinetics in rats.

摘要

研究了过氧化氢酶调节剂(氨基三唑、醋酸铅、牛磺酸、邻苯二甲酸二(2-乙基己基)酯)对乙醇偏好性、其药代动力学以及大鼠肝脏和大脑中乙醇及乙醛代谢酶活性的影响。醋酸铅(100mg/kg,腹腔注射,7天)、氨基三唑(1g/kg,腹腔注射,7天)和牛磺酸(650mg/kg,灌胃,14天)在自由选择(10%乙醇水溶液)条件下降低了乙醇摄入量,而邻苯二甲酸二(2-乙基己基)酯(300mg/kg,灌胃,7天)对该参数没有任何影响。牛磺酸、醋酸铅和邻苯二甲酸二(2-乙基己基)酯显著激活了肝脏乙醇脱氢酶、微粒体乙醇氧化系统和过氧化氢酶过氧化物酶活性。氨基三唑也激活了乙醇脱氢酶和微粒体乙醇氧化系统,但抑制了肝脏过氧化氢酶。这种处理对肝脏和大脑中醛脱氢酶以及过氧化氢酶的活性影响不显著。醋酸铅、邻苯二甲酸二(2-乙基己基)酯和氨基三唑连续7天给药显著影响了乙醇(2g/kg,腹腔注射)的药代动力学参数:药代动力学曲线下面积和消除半衰期显著降低,而消除常数和清除率增加。这明确表明乙醇消除加速。牛磺酸连续14天摄入对大鼠乙醇药代动力学参数影响不显著。

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