Reversal of toxicity using avidin-based hemoperfusion: a model system in rats using biotinylated melittin.
The high-affinity interaction between avidin and biotin (Kd = 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/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.
Britt
A M
AM
Center for Emergency Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, USA.
Burkhart
K K
KK
Billingsley
M L
ML
D000818:Animals; D001360:Avidin / Q000737:chemistry*; D001710:Biotin / Q000737:chemistry*; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D006464:Hemoperfusion; D008297:Male; D008555:Melitten / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001360:Avidin; D008555:Melitten; D001710:Biotin