Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Beijing Institute of Radiation Medicine, Beijing, China.
J Ethnopharmacol. 2018 Oct 28;225:81-89. doi: 10.1016/j.jep.2018.07.001. Epub 2018 Jul 2.
Aristolochia manshuriensis Kom (AMK), belonging to the Aristolochia family, is traditionally used in China to remove heart fire, promote dieresis, restore menstruation, and enhance milk secretion. The active constitutes of AMK are aristolochic acids (AAs, I and II) that are reported to cause serious side effects including nephrotoxicity and carcinogenicity.
The tumorigenic role of AMK is far to be understood. We analyzed the toxicity reactions after long-term exposure of AMK in rats.
Sprague-Dawley rats underwent gavage with AMK doses of 51 mg/kg (AMK-1), 253 mg/kg (AMK-2), 508 mg/kg (AMK-3), 1029 mg/kg (AMK-4) or AAs of 15 mg/kg (AAs), and then sacrificed at the 6th, 10th, 14th, 18th, 22th, 26th and 30th weeks. Endpoint measurements included clinical observations, body weights, blood biochemistry, haematology and histomorphological observations.
Body weight decreased after AMK or AAs treatment in rats. AMK destroyed renal function, and induced anemia in rats. AMK caused kidney, stomach, bladder and subcutaneous tumors in rats. In addition, primary hepatic carcinoma was not observed in rats.
AMK had significant toxic effects in rats with regard to decreased body weight, diminished renal function, increased anemia and tumor incidence. Kidney, stomach, bladder and subcutaneous tissue are carcinogenic target organs of AMK or AAs, however liver is no- carcinogenic target organ of AMK or AAs in rats. AMK is carcinogenic in rats, and not be safe for humans.
马兜铃科植物东北马兜铃(AMK),传统上用于中国,以去除心火,促进利尿,恢复月经,促进乳汁分泌。AMK 的活性成分是马兜铃酸(AA,I 和 II),据报道会引起严重的副作用,包括肾毒性和致癌性。
AMK 的致癌作用还远未被理解。我们分析了 AMK 在大鼠体内长期暴露后的毒性反应。
Sprague-Dawley 大鼠经口灌胃给予 AMK 剂量分别为 51mg/kg(AMK-1)、253mg/kg(AMK-2)、508mg/kg(AMK-3)、1029mg/kg(AMK-4)或 15mg/kg AA(AAs),然后在第 6、10、14、18、22、26 和 30 周处死。终点测量包括临床观察、体重、血液生化、血液学和组织形态学观察。
AMK 或 AAs 处理后大鼠体重下降。AMK 破坏肾功能,并导致大鼠贫血。AMK 导致大鼠肾脏、胃、膀胱和皮下肿瘤。此外,未观察到大鼠原发性肝癌。
AMK 对大鼠具有显著的毒性作用,表现为体重下降、肾功能减退、贫血和肿瘤发生率增加。肾脏、胃、膀胱和皮下组织是 AMK 或 AAs 的致癌靶器官,而肝脏不是 AMK 或 AAs 的致癌靶器官。AMK 在大鼠中具有致癌性,对人类不安全。