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1、Toxicology 198 (2004) 195–201Studies on the toxicity of Aristolochia manshuriensis (Guanmuton)?Shi-Lin Hu a,?, Hong-Qi Zhang b, Kelvin Chan b, Quan-Xi Mei ca Institute of Chinese Material Medica, China Academy of Traditi

2、onal Chinese Medicine, Beijing 100700, China b School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China c Zhongshan Hospital of Traditional Chinese Medicine, Zhongshan, Guangdong Province, ChinaAbstract

3、Aims: (1) To study the acute and chronic toxicity of stem of Aristolochia manshuriensis (AMA Guanmuton) which is a Chinese medicinal herb in order to provide basis for safe clinical use. (2) To investigate the possibilit

4、y of reducing toxicity of the herb combined with Rhizoma Coptidis (Huanglian). Methods: The 70% ethanol extract of the herb was fed to mice via gastric tube for 8 weeks. The blood was collected to assess liver and renal

5、functions. The tissue samples of the liver, kidney and bladder were collected from executed animals for pathology examination. Results: The LD50 with a 95% average trustable probability (P = 0.95) of AMA from Hanzhong (H

6、Z) is 29.2 ± 3.71 g/kg. The weight of animals in the treatment group at a dose of 4 g/kg raw drug, equivalent to 40 times of normal human dose in clinical prescription, remained the same as the control group (P >

7、 0.05). On pathological examination, there were no morphological changes under light microscope in the liver and bladder. For the kidney, the renal toxicity was significantly reduced after using ethanol extract of R. cop

8、tidis to process HZ AMA in that there were no interstitial inflammation, formation of hyaline cast or regeneration of renal tubules. © 2004 Published by Elsevier Ireland Ltd.Keywords: Herbal safety; Arisolochic acid

9、; Aristolochia manshuriensis1. IntroductionThe stem of Aristolochia manshuriensis Kom. (AMA, Guanmuton) is a traditional Chinese medicinal herb mainly harvested from the Northeast of China. It has been used widely for th

10、ousands years in China and other countries. In 1983, as an example from a survey conducted 20 years ago, the domestic sale of Guanmuton was 320 t. This implied that, based on 6 g? Supported by Hong Kong Baptist Universit

11、y FRG/00-01/II-81. ? Corresponding author. Tel.: +86-10-64012317; fax: +86-10-64012317. E-mail address: h5horse5@163.com (S.-L. Hu).per day with a 10 day course, there would be about 5.3 million people using it. It could

12、 imply, based on this account, that there would be 6400 t of Guanmuton consumed over the last 20 years involving 1 billion patients. The export of the herb to Japan and South- east Asia countries was about 20 t per year

13、(CMM, 1995). Despite this large consumption, however, the incidence of renal carcinoma that might not be related to Guanmuton in China is 3.5% within all cancers, lower than that of the 4% world-wide average and most Wes

14、tern countries (Li, 2001). From the epidemi- ological point of view, there is no evidence for the association between the use of Guanmuton (AMA) and carcinogenesis in the urinary tract in China.0300-483X/$ – see front ma

15、tter © 2004 Published by Elsevier Ireland Ltd. doi:10.1016/j.tox.2004.01.026S.-L. Hu et al. / Toxicology 198 (2004) 195–201 197(3) HZL, 1 g/kg per day (i.e. 0.1 g/1 ml/100 g per day); (4) HZP, 2 g/kg per day; (5) JL

16、L, 1 g/kg per day; (6) SXL, 1 g/kg per day; (7) HZC, 2 g/kg per day; (8) Control group (CON), distill water 1 ml/100 g per day.At the first and the eighth weeks, blood samples were collected from retroocular venous plexu

17、s (1– 2 ml) for biochemical examinations. At week 8, 10 rats from each group were sacrificed and their organs (liver, kidney and bladder) were collected for patho- logical examination. The remaining mice stopped to take

18、the herbal medicines from week 9, and were sac- rificed at week 10 for collection of blood and organ samples. Blood tests including ALT, AST, total bilirubin, al- bumin, creatinine (Cr) and BUN were performed. The collec

19、ted tissue samples were prepared routinely, andTable 1 LD50 of Aristolochia manshuriensis (HZ)Group N Dose (g/kg) Lgd (x) Death Mortality (p) P21 10 160 2.204 (d1, xm) 10 1 2 10 112 2.049 (d2) 10 1 3 10 78 1.892 (d3) 10

20、1 4 10 55 1.740 (d4) 10 1 1 5 10 38 1.580 (d5) 9 0.9 0.81 6 10 27 1.431 (d5) 3 0.3 0.09Note: LD50 from the last three groups is 29.2 g/kg with a 95% trustable limit 29.2 ± 3.71 g/kg.Table 2 ALT changes (U/l)Time n C

21、ON HZC HZP YQL JLL HZL HZM HZH0 n = 16 57.9 ± 12.7 61.9 ± 13.1 56.6 ± 9.6 57.9 ± 12.2 48.9 ± 8.9 55.2 ± 8.5 58.5 ± 9.5 49.6 ± 15.1 8 n = 12 40.5 ± 8.7 59.2 ± 16.3?? 42.0

22、± 12.3 40.7 ± 7.8 36.6 ± 7.3 34.3 ± 7.8 37.9 ± 8.6 53.8 ± 14.0?10 n = 6 37.7 ± 3.9 44.7 ± 8.4 39.6 ± 13.6 42.8 ± 16.7 55.8 ± 31.7 43.9 ± 11.1 39.0 ± 6.6 45

23、.2 ± 9.3Note: comparing with the control group (CON). ? P 0.05). At early stage there were casualties that were shown by autopsy to be caused by technical errors in tube feeding instead of by drug toxicity. At late

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