马兜铃酸(1:1MIXTUREOFARISTOLOCHICACIDIANDARISTOLOCHICACIDII) | 67123-64-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 中文名称: 马兜铃酸(1:1MIXTUREOFARISTOLOCHICACIDIANDARISTOLOCHICACIDII)
• 中文别名: 马兜铃酸A；增噬力酸；8-甲氧基-3,4-亚甲二氧基-10-硝基菲-1-甲酸；氧环菲甲酸；马兜铃酸
• 英文名称: Phenanthro(3,4-d)-1,3-dioxole-5-carboxylic acid, 8-methoxy-6-nitro-, 6-nitrophenanthro(3,4-d)-1,3-dioxole-5-carboxylate (2:1)
• 英文别名: 8-methoxy-6-nitronaphtho[2,1-g][1,3]benzodioxole-5-carboxylic acid;6-nitronaphtho[2,1-g][1,3]benzodioxole-5-carboxylic acid
• CAS: 67123-64-2
• 化学式: C50H31N3O20
• 分子量: 993.8
• InChiKey: FGGYSLIDOXIJNP-UHFFFAOYSA-N

物化性质

• 熔点：
  260-265 °C
• 溶解度：
  可溶于DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  10.0
• 重原子数：
  73
• 可旋转键数：
  5
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  323
• 氢给体数：
  3
• 氢受体数：
  20

ADMET

代谢

在对雄性Wistar大鼠口服马兜铃酸I和II的广泛研究中（给予纯化合物；3毫克），在尿液和粪便中检测到了以下代谢物：来自马兜铃酸I的有马兜铃内酰胺I、马兜铃内酰胺Ia、马兜铃酸Ia、马兜铃酸I以及3,4-亚甲二氧基-8-羟基-1-菲甲酸；来自马兜铃酸II的有马兜铃内酰胺II、马兜铃内酰胺Ia以及3,4-亚甲二氧基-1-菲甲酸。/马兜铃酸I和II/

In an extensive study following oral administration of aristolochic acids I and II to male Wistar rats (pure compounds given; 3 mg), the following metabolites were detected in urine and feces: from aristolochic acid I -- aristolactam I, aristolactam Ia, aristolochic acid Ia, aristolic acid I and 3,4-methylenedioxy-8-hydroxy-1-phenanthrenecarboxylic acid; from aristolochic acid II -- aristolactam II, aristolactam Ia and 3,4-methylenedioxy-1-phenanthrenecarboxylic acid. /Aristolochic Acid I and II/

来源:Hazardous Substances Data Bank (HSDB)

代谢

六名健康志愿者连续几天每天服用0.9毫克的混合了马兜铃酸I和II的剂量（可能是口服，但没有明确说明），并从第三天的24小时尿样中分析代谢物。检测到的唯一代谢物是马兜铃内酰胺I（马兜铃酸I的代谢物）和马兜铃内酰胺II（马兜铃酸II的代谢物）。这两种代谢物的转化百分比没有报告。这与之前关于马兜铃酸在人体内口服吸收后未经改变的化合物在尿液、胆汁、母乳和脑脊液中排出的报告相矛盾。

... Six healthy volunteers were given a daily dose (presumably oral but not explicitly state) of 0.9 mg of a mixture of aristolochic acids I and II (ratio not specified) for several days, and 24 hour urine samples from day 3 of this trial were analysed for metabolites. The only metabolites detected were aristolactam I (metabolite of aristolochic acid I) and aristolactam II (metabolite of aristolochic acid II). The percentage conversions to these two metabolites were not reported. This contradicts and earlier report of oral absorption of aristolochic acid in humans resulting in the compound(s) being excreted unchanged in urine, bile, breast milk and cerebrospinal fluid.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对于天然存在的马兜铃酸混合物的致癌性，人类中的证据有限。在实验动物中，对于马兜铃酸致癌性的证据是充分的。总体评估：天然存在的马兜铃酸混合物对人类可能是致癌的（2A组）。

Evaluation: There is limited evidence in humans for the carcinogenicity of naturally occuring mixtures of aristolochic acids. There is sufficient evidence in experimental animals for the carcinogenicity of aristolochic acids. Overall evaluation: Naturally occurring mixtures of aristolochic acids are probably carcinogenic to humans (Group 2A).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：有足够的人类证据表明含有马兜铃属植物种类的草药具有致癌性。目前还没有实验动物数据关于含有马兜铃属植物种类的草药的致癌性。总体评估：含有马兜铃属植物种类的草药对人类具有致癌性（第1组）。/含有马兜铃属植物种类的草药/

Evaluation: There is sufficient evidence in humans for the carcinogenicity of herbal remedies containing plant species of the genus Aristolochia. There is no data in experimental animals on the carcinogenicity of herbal remedies containing plant species of the genus Aristolochia. Overall evaluation: Herbal remedies containing plant species of the genus Aristolochia are carcinogenic to humans (Group 1). /Herbal remedies containing plant species of the genus Aristolochia/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在这项研究中，探讨了 aristolochic 酸（AA）在大鼠中诱导肿瘤的发展，并研究了是否加入二烯丙基硫化物（DAS）的影响。实验还进行了确定 DAS 管理对 AA 衍生的 DNA 单链区域和 DNA 加合物在大鼠前胃形成的影响。在雄性 BD-6 大鼠口服处理 AA 12 周后（2 x 10 mg/kg/周），诱导出了前胃、膀胱和胸腺肿瘤。在 AA 处理前 4 小时通过胃内给药 150 mg/kg DAS 显著减少了发展前胃肿瘤的大鼠数量（实验开始后 6-9 个月）。当 DAS 与 AA 联合给药时，AA 诱导的前胃肿瘤发生率为 10%（20 只大鼠中有 2 只），而单独给药 AA 时为 60%（20 只动物中有 12 只）。高剂量的 DAS（2 x 150 mg/kg）显著抑制了前胃鳞状细胞癌的形成。然而，硫醚并未阻止前胃和膀胱乳头状瘤的形成。此外，DAS 联合给药减少了大鼠前胃 DNA 中单链区域的积累。使用 32P-后标记分析的核酸酶 P1 增强方法，也检测到了在 DAS 联合给药后 AA 衍生的加合物水平降低。我们得出结论，DAS 联合给药后 DNA 损伤的减少与乳头状瘤转化为恶性前胃肿瘤的延迟有关。

In this study the development of aristolochic acid (AA) induced tumors in rats with and without diallyl sulfide (DAS) was studied. Experiments were also conducted to establish the effects of DAS administration on AA-derived DNA single-stranded regions and DNA adduct formation in the forestomach of such animals. Forestomach, urinary bladder and thymus tumors were induced in male BD-6 rats after oral treatment for 12 weeks with AA (2 x 10 mg/kg/week). Administration of 150 mg/kg DAS intragastrically 4 h prior to AA treatment reduced significantly the number of rats that developed forestomach tumors (6-9 months after the start of experiment). The incidence of AA-induced forestomach tumors was 10% (two out of 20 rats) after co-administration of DAS and 60% (12 out of 20 animals) when AA was administered alone. The high dose of DAS (2 x 150 mg/kg) markedly inhibited the formation of squamous cell carcinomas in the forestomach. However, the thioether did not prevent the formation of forestomach and urinary bladder papillomatosis. Additionally, DAS co-administration decreased the accumulation of single-stranded regions in rat forestomach DNA. Using the nuclease P1 enhancement method of the 32P-postlabeling assay, a decrease in the level of AA-derived adducts was also detected after co-administration of DAS. We conclude that the decrease of DNA damage after DAS co-administration is associated with the delay in conversion of papillomas to malignant forestomach tumors.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道。如有必要，进行吸痰。观察呼吸不足的迹象，并在需要时辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，并在必要时进行治疗……。监测休克，并在必要时进行治疗……。预期癫痫发作，并在必要时进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中用生理盐水连续冲洗每只眼睛……。不要使用催吐剂。对于误食，如果患者能吞咽、有强烈的呕吐反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于昏迷、严重肺水肿或呼吸停止的患者，考虑进行口咽或鼻咽插管以控制气道。使用带有气囊面罩的装置进行正压通气技术可能有益。监测心率和必要时治疗心律失常。 ... 开始静脉输液，使用5%葡萄糖盐水/生理盐水： "保持通路开放"，最低流速/。如果出现低血容量的迹象，使用乳酸钠林格氏液。注意液体过载的迹象。考虑使用药物治疗肺水肿。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象。 ... 使用地西泮（安定）治疗癫痫。使用丙美卡因氢氯化物协助眼部冲洗。 /毒药A和B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  T
• 安全说明：
  S35,S45,S7
• 危险类别码：
  R25