Continuous intravenous infusion of deferoxamine reduces mortality by paraquat in vitamin E-deficient rats.
Paraquat, an oxygen radical-generating agent, is a widely used agrochemical that is also toxic for humans, in whom it may cause respiratory failure. In the present study, we investigated the effect of deferoxamine (DF), an iron chelator with antioxidant capacity, on paraquat toxicity in vitamin E-deficient rats. After the administration of paraquat at a dose of 20 mg/kg the animals were treated with a continuous intravenous infusion of DF for 14 days. In a dose-response study, four of six animals receiving 100 mg DF/kg/24 h survived the study period of 14 days compared with none in the saline-treated control group (n = 6), and three and two animals in the groups receiving 50 (n = 6) and 200 mg DF/kg/24 h (n = 6), respectively. In another series of experiments, animals were monitored for a total period of 35 days, at which time any survivors were killed, and lung histologic examination was carried out. Deferoxamine treatment was started simultaneously (n = 21), 6 h (n = 18), and 16 h (n = 18) after paraquat poisoning. Percent survival in the various time-point groups was 47.7 (p less than 0.01), 38.9 (p less than 0.02), and 22.2 (not significant), respectively, compared with 7.1 (n = 14) in the control group. The presence of lung damage was seen only in those of the surviving rats where DF was started at the 16 h time point after paraquat administration. In ancillary in vitro studies, where Escherichia coli was used as a source of enzymic activity for the redox-cycling of paraquat, DF completely inhibited the formation of hydroxyl radical (.OH).(ABSTRACT TRUNCATED AT 250 WORDS)
van Asbeck
B S
BS
Department of Medicine, University Hospital, Utrecht, The Netherlands.
Hillen
F C
FC
Boonen
H C
HC
de Jong
Y
Y
Dormans
J A
JA
van der Wal
N A
NA
Marx
J J
JJ
Sangster
B
B
D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D007260:Infusion Pumps; D008168:Lung / Q000473:pathology; D008297:Male; D009026:Mortality; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000506:poisoning*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014811:Vitamin E Deficiency / Q000503:physiopathology*
D003676:Deferoxamine; D010269:Paraquat