Dose-dependent reversal of acute murine colchicine poisoning by goat colchicine-specific Fab fragments

Toxicology. 1991;68(2):121-32. doi: 10.1016/0300-483x(91)90015-s.

Abstract

The use of colchicine-specific Fab fragments is of interest in human poisoning. In the present study, we show the efficacy of Fab fragments in reversing colchicine toxicity in mice. High affinity antibodies (Ka = 2 x 10(10) M-1) against colchicine were raised in goats; Fab fragments were purified by DEAE chromatography after papain hydrolysis of IgG. Mice were intoxicated with a 100% lethal colchicine dose (3.8 mg/kg). When a half molar dose (M/2) of Fab fragments in relation to the colchicine dose was intravenously and intraperitoneally administered 90 min after colchicine infusion using a multiple dosage schedule, 80% of the Fab-treated mice survived compared to the control group which did not receive Fab fragments (P less than 0.01). Using a M/4 and M/8 dose of Fab fragments, the mortality was respectively 50% and 80%. The dose-effect relationship was linear (r = 0.99). Delayed administration of a M/2 dose of Fab fragments 6 h after colchicine administration resulted in 50% survival (P less than 0.01). Body temperature and body weight were selective markers of the severity of the intoxication. In the control group, a marked decrease of body temperature was observed following the first few hours after the intoxication (-21% compared to basal value 48 h after colchicine). In the Fab-treated group, the decrease was inversely related to the Fab fragment dose. Body temperature returned to the basal values 7 days after intoxication. A progressive decrease in body weight was concomitantly observed in intoxicated mice until death, while values returned to baseline 9 days after colchicine in surviving Fab-treated mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites, Antibody
  • Body Weight / drug effects
  • Chromatography, Gel
  • Chromatography, Ion Exchange
  • Colchicine / immunology
  • Colchicine / poisoning*
  • Electrophoresis, Cellulose Acetate
  • Electrophoresis, Polyacrylamide Gel
  • Goats
  • Hypothermia / chemically induced
  • Hypothermia / therapy
  • Immunization, Passive
  • Immunoglobulin Fab Fragments / biosynthesis
  • Immunoglobulin Fab Fragments / isolation & purification
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Male
  • Mice
  • Poisoning / therapy

Substances

  • Immunoglobulin Fab Fragments
  • Colchicine