Acrylamide and glycidamide in plasma of diabetic and non-diabetic rats, a comparative toxicokinetic study

Asieh Karimani, G. Karimi, Amirhosein Mohammadpour
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Abstract

Abstract Acrylamide is converted to glycidamide as a reactive metabolite by the monooxygenase isozyme CYP2E1. Since the latter is known to be induced in diabetic patients, increased acrylamide toxicity in such patients is suspected. Differences in acrylamide toxicokinetics in non-diabetic and diabetic rats receiving acrylamide (50 mg/kg) orally or via i.p. injection were investigated in this report. Blood was collected at various time points, acrylamide and glycidamide in plasma were determined by reversed-phase high-performance liquid chromatography, and the data were analyzed for toxicokinetic parameters using the proper software. Mean maximum plasma concentration, the apparent clearance, and area under the curve in non-diabetic rats were significantly higher than in diabetics, an important fact to be considered in xenobiotic exposure of diabetic individuals.
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糖尿病大鼠与非糖尿病大鼠血浆中丙烯酰胺和丙烯酰胺的毒性动力学比较研究
丙烯酰胺作为一种反应性代谢产物被单加氧酶同工酶CYP2E1转化为甘油酰胺。由于已知后者可在糖尿病患者中诱发,因此怀疑这类患者中丙烯酰胺毒性增加。研究了非糖尿病大鼠和糖尿病大鼠口服丙烯酰胺(50 mg/kg)和腹腔注射丙烯酰胺后丙烯酰胺毒性动力学的差异。采集各时间点血液,采用反相高效液相色谱法测定血浆中丙烯酰胺和丙烯酰胺的含量,并采用相应的软件对数据进行毒理动力学参数分析。非糖尿病大鼠的平均最大血浆浓度、表观清除率和曲线下面积显著高于糖尿病大鼠,这是糖尿病个体接触外源性药物时需要考虑的一个重要事实。
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