title: Dose-dependent reversal of acute murine colchicine poisoning by goat colchicine-specific Fab fragments.
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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U26, Hôpital Fernand Widal, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Sabouraud
authors.forename: M
authors.initials: M
authors.lastname: Urtizberea
authors.forename: M
authors.initials: M
authors.lastname: Grandgeorge
authors.forename: P
authors.initials: P
authors.lastname: Gattel
authors.forename: M E
authors.initials: ME
authors.lastname: Makula
authors.forename: J M
authors.initials: JM
authors.lastname: Scherrmann
mesh_terms: D000818:Animals; D001666:Binding Sites, Antibody; D001835:Body Weight / Q000187:drug effects; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003078:Colchicine / Q000276:immunology / Q000506:poisoning*; D004588:Electrophoresis, Cellulose Acetate; D004591:Electrophoresis, Polyacrylamide Gel; D006041:Goats; D007035:Hypothermia / Q000139:chemically induced / Q000628:therapy; D007116:Immunization, Passive; D007140:Immunoglobulin Fab Fragments / Q000096:biosynthesis / Q000302:isolation & purification / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D011041:Poisoning / Q000628:therapy
chemical_list: D007140:Immunoglobulin Fab Fragments; D003078:Colchicine