Reversal of toxicity using avidin-based hemoperfusion: A model system in rats using biotinylated melittin

Andres M. Britt, Keith K. Burkhart, Melvin Billingsley

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Abstract

The high-affinity interaction between avidin and biotin (Kd = 10-15M) 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/1 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.

Original languageEnglish (US)
Pages (from-to)307-312
Number of pages6
JournalPharmacology
Volume50
Issue number5
DOIs
Publication statusPublished - Jan 1 1995

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All Science Journal Classification (ASJC) codes

  • Pharmacology

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