REVERSAL OF TOXICITY USING AVIDIN-BASED HEMOPERFUSION - A MODEL SYSTEM IN RATS USING BIOTINYLATED MELITTIN
REVERSAL OF TOXICITY USING AVIDIN-BASED HEMOPERFUSION - A MODEL SYSTEM IN RATS USING BIOTINYLATED MELITTIN
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DOI：
10.1159/000139296
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发表时间：
1995-05-01
期刊：
影响因子：
3.1
通讯作者：
BILLINGSLEY, ML
中科院分区：
文献类型：
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作者：
BRITT, AM;BURKHART, KK;BILLINGSLEY, ML
亲和素和生物素之间的高亲和力相互作用（K-d = 10(-15) M）可用于开发从生物体液中提取生物素化药物和毒物的特定方案。蜂毒是蜂毒的主要毒性成分，被生物素化，并被用作模型毒物，以确定基于亲和素的体外血液灌流是否可以去除生物素化的蜂毒，从而改变大鼠的毒性反应的严重程度。用n -羟基琥珀酰亚胺-长链生物素对蜂鸟素进行生物素化。连续四次静脉注射1.7 mg/kg生物素化蜂毒素（0、5、20和35分钟），120分钟后，生物素化蜂毒素对大鼠产生100%的致死率。构建亲和素血液灌流柱（10 mg /l ml凝胶），经股血管与生物素化蜂毒素中毒大鼠连接。对照大鼠采用d-生物素阻断的亲和素柱进行血液灌注。生物素阻断的亲和素柱对照组6只大鼠无一存活，而9只实验大鼠中有5只存活至120分钟。两组生存率差异有统计学意义（p < 0.0048）。因此，基于亲和素的血液灌流改善了生物素化蜂毒毒性后的生存，并加强了基于亲和素的血液灌流可以逆转生物素化毒性的概念。
The high-affinity interaction between avidin and biotin (K-d = 10(-15) M) can be exploited to develop specific protocols for retrieval of biotinylated drugs and toxicants from biological fluids. Melittin, the main toxic component of bee venom, was biotinylated and used as a model toxicant to determine whether avidin-based extracorporeal hemoperfusion could remove biotinylated melittin and thus alter the severity of the toxic response in rats. Melittin was biotinylated using N-hydroxysuccinimide-long-chain biotin. Biotinylated melittin produced 100% lethality in rats by 120 min following four sequential intravenous injections of 1.7 mg/kg biotinylated melittin (0, 5, 20, and 35 min). An avidin hemoperfusion column was constructed (10 mg avidin/l ml gel) and connected via the femoral vasculature to rats intoxicated with biotinylated melittin. Controls rats were hemoperfused using avidin columns blocked with d-biotin. None of the 6 rats hemoperfused using the biotin-blocked avidin column control survived, whereas 5 of 9 of the experimental rats survived to 120 min. The difference between the two survival rates was statistically significant (p < 0.0048). Thus, avidin-based hemoperfusion improved survival following biotinylated melittin toxicity and strengthens the concept that avidin-based hemoperfusion can reverse the toxicity of biotinylated toxicants.