Mengs U, Grimminger W, Krumbiegel G, Schuler D, Silber W, Völkner W
Madaus, Ostmerheimer Strasse 198, D-51109, Cologne, Germany.
Mutat Res. 1999 Aug 18;444(2):421-6. doi: 10.1016/s1383-5718(99)00115-1.
In previous studies, an analytically well-defined senna extract, commonly used as a laxative, gave positive responses in vitro in the Ames test and in the CHO assay. Therefore, the objective of this study was to investigate the genotoxic activity of the same senna extract in an in vivo genotoxicity assay by means of the generally acknowledged MNT. After administration of an oral dose of 2000 mg senna extract/kg to NMRI mice of both genders, which is equivalent to 119 mg potential rhein/kg, 5.74 mg potential aloeemodin/kg and 0. 28 mg potential emodin/kg, there were no elevated levels of micronuclei in bone marrow cells. Kinetic studies were performed in parallel to demonstrate target organ availability. Highest concentrations in the plasma were reached after 1 h with 3.4 microg rhein/ml and 0.065 microg aloeemodin/ml. In all cases, emodin was below the limit of quantification. From the results, the in vitro clastogenic activity of the senna extract could not be confirmed in the mouse micronucleus assay. Together with further negative in vivo genotoxicity studies with anthranoids, the conclusion can be drawn that there is no indication so far demonstrating a genotoxic risk for patients taking senna laxatives.
在先前的研究中，一种分析定义明确的番泻叶提取物（常用作泻药）在体外Ames试验和CHO试验中给出了阳性反应。因此，本研究的目的是通过普遍认可的微核试验（MNT），在体内遗传毒性试验中研究同一种番泻叶提取物的遗传毒性活性。向两种性别的NMRI小鼠口服剂量为2000 mg番泻叶提取物/kg（相当于119 mg潜在大黄酸/kg、5.74 mg潜在芦荟大黄素/kg和0.28 mg潜在大黄素/kg）后，骨髓细胞中的微核水平没有升高。同时进行了动力学研究以证明靶器官的可利用性。给药1小时后血浆中达到最高浓度，大黄酸为3.4 μg/ml，芦荟大黄素为0.065 μg/ml。在所有情况下，大黄素均低于定量限。从结果来看，番泻叶提取物的体外致断裂活性在小鼠微核试验中未得到证实。连同对蒽醌类化合物进一步的阴性体内遗传毒性研究，可以得出结论：目前没有迹象表明服用番泻叶泻药的患者存在遗传毒性风险。
