TY - JOUR
PY - 1991//
TI - Dose-dependent reversal of acute murine colchicine poisoning by goat colchicine-specific Fab fragments
JO - Toxicology
A1 - Sabouraud, A.
A1 - Urtizberea, M.
A1 - Grandgeorge, M.
A1 - Gattel, P.
A1 - Makula, M. E.
A1 - Scherrmann, J. M.
SP - 121
EP - 132
VL - 68
IS - 2
N2 - 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. Language: en
LA - en
SN - 0300-483X
UR - http://dx.doi.org/
ID - ref1
ER -