Brubacher J R, Lachmanen D, Ravikumar P R, Hoffman R S
Department of Emergency Medicine, Vancouver Hospital and Health Sciences Centre, British Columbia Drug and Poison Information Centre, Canada.
Toxicon. 1999 Jun;37(6):931-42. doi: 10.1016/s0041-0101(98)00224-4.
Chan Su, a traditional Chinese medication, and Love Stone, a topical aphrodisiac, are both made from dried venom of the toad bufo bufo gargarizans and contain bufalin, cinobufotalin, cinobufagin, and other cardioactive steroids of the bufadienolide class. Deaths have occurred following ingestion of these products and the clinical course resembles digoxin toxicity. The purpose of this study was to determine the efficacy of digoxin specific Fab fragments in treating Chan Su poisoning. An ethanolic extract was prepared from Chan Su. Digoxin specific Fab fragments were reconstituted in normal saline to a concentration of 80 mg/ml. An approximate LD90 dose was determined in preliminary experiments. Mice were then randomly divided into a treatment group of 15 mice and a control group of 30 mice. The treatment group was pretreated with 20 ml/kg of digoxin specific Fab fragment solution by intraperitoneal injection at t = 0, followed by 10 ml/kg of digoxin specific Fab fragments intraperitoneal at t = 30 min. The control group was pretreated with equal volumes of intraperitoneal normal saline at the same times. Immediately following the 30 min injection, both groups were given the estimated LD90 dose of Chan Su extract by subcutaneous injection. An endpoint of survival at 6 h was chosen after preliminary results showed that all deaths occurred in the first 4 h. All 30 of the control mice had seizures followed by death compared to 11 seizures and 7deaths in the 15 treatment mice. These results were statistically significant by Fisher's exact test (p = 0.00003 for mortality and p = 0.009 for seizures). Digoxin specific Fab fragments are effective in the treatment of Chan Su poisoning in mice and may be effective for poisoning by other cardioactive steroids of the bufadienolide class.
蟾酥是一种传统中药,而“情石”是一种外用壮阳药,二者均由中华大蟾蜍的干毒液制成,含有蟾力苏、华蟾酥毒基、华蟾酥精以及其他蟾蜍二烯羟酸内酯类的强心甾体。摄入这些产品后曾发生死亡事件,临床过程类似于地高辛中毒。本研究的目的是确定地高辛特异性Fab片段治疗蟾酥中毒的疗效。从蟾酥中制备了乙醇提取物。将地高辛特异性Fab片段用生理盐水复溶至浓度为80mg/ml。在初步实验中确定了近似的LD90剂量。然后将小鼠随机分为15只小鼠的治疗组和30只小鼠的对照组。治疗组在t = 0时通过腹腔注射20ml/kg的地高辛特异性Fab片段溶液进行预处理,随后在t = 30分钟时腹腔注射10ml/kg的地高辛特异性Fab片段。对照组在相同时间用等量的腹腔生理盐水进行预处理。在30分钟注射后,立即给两组皮下注射估计的LD90剂量的蟾酥提取物。初步结果显示所有死亡均发生在最初4小时后,选择6小时的生存终点。30只对照小鼠均出现惊厥继而死亡,相比之下,15只治疗小鼠中有11只出现惊厥,7只死亡。通过Fisher精确检验,这些结果具有统计学意义(死亡率p = 0.00003,惊厥p = 0.009)。地高辛特异性Fab片段对小鼠蟾酥中毒治疗有效,可能对其他蟾蜍二烯羟酸内酯类强心甾体中毒也有效。