Cosyns J P, Goebbels R M, Liberton V, Schmeiser H H, Bieler C A, Bernard A M
Department of Pathology, ANPS 1712 Catholic University of Louvain Medical School, Cliniques Universitaires St. Luc, Brussels, Belgium.
Arch Toxicol. 1998 Nov;72(11):738-43. doi: 10.1007/s002040050568.
Chinese herbs nephropathy (CHN), a rapidly progressive interstitial fibrosis of the kidney, has been described in approximately 100 young Belgian women who had followed a slimming regimen containing some Chinese herbs. In 4 patients multifocal transitional cell carcinomas (TCC) were observed. Aristolochic acid (AA), suspected as the causal factor of CHN, is a well known carcinogen but its ability to induce fibrosis has never been demonstrated. The objective of this study was to evaluate the latter using doses of AA, durations of intoxication and delays of sacrifice known to yield tumours in rats. We also tested the hypothesis that a possible fibrogenic role of AA was enhanced by the other components of the slimming regimen. Male and female rats were treated orally with 10 mg isolated AA/kg per day for 5 days/week, or with approximately 0.15 mg AA/ kg per day 5 days/week contained in the herbal powder together with the other components prescribed in the slimming pills for 3 months. The animals were killed respectively 3 and 11 months later. At sacrifice, animals in both groups had developed the expected tumours but not fibrosis of the renal interstitium. Whether the fibrotic response observed in man is due to species and/or strain related differences in the response to AA or to other factors, remains to be determined. Interestingly, despite the addition of fenfluramine and diethylpropion, two drugs incriminated in the development of valvular heart disease, no cardiac abnormalities were observed.
中草药肾病(CHN)是一种迅速进展的肾间质纤维化疾病,在约100名服用含某些中草药减肥疗法的年轻比利时女性中有所报道。在4名患者中观察到了多灶性移行细胞癌(TCC)。马兜铃酸(AA)被怀疑是CHN的致病因素,它是一种众所周知的致癌物,但其诱导纤维化的能力从未得到证实。本研究的目的是使用已知能在大鼠身上诱发肿瘤的AA剂量、中毒持续时间和处死延迟时间来评估后者。我们还检验了这样一种假设,即减肥疗法的其他成分会增强AA可能的促纤维化作用。雄性和雌性大鼠分别接受以下处理:每天口服10毫克分离的AA/千克,每周5天,持续5天;或每天口服约0.15毫克AA/千克,每周5天,持续3个月,该剂量的AA包含在草药粉末中,并与减肥药中规定的其他成分一起服用。动物分别在3个月和11个月后处死。处死时,两组动物均出现了预期的肿瘤,但未出现肾间质纤维化。人类中观察到的纤维化反应是由于对AA反应的物种和/或品系相关差异,还是由于其他因素,仍有待确定。有趣的是,尽管添加了右芬氟拉明和二乙胺苯丙酮这两种与瓣膜性心脏病发生有关的药物,但未观察到心脏异常。