Continuous Intravenous Infusion of Deferoxamine Reduces Mortality by Paraquat in Vitamin E-deficient Rats

Abstract

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)

Use of Iron Chelators in Preventing Hydroxyl Radical Damage: Adult Respiratory Distress Syndrome as an Experimental Model for the Pathophysiology and Treatment of Oxygen-Radical-Mediated Tissue Damage

“…Survival of con trol rats, at 35 days after an i.v. paraquat dose of 20 mg/ kg, was only 7%, while 48% of the animals survived if DFO infusion started at the moment of PQ2+ injection, and 39% if DFO was started 6 h later [155], In rats with a normal vitamin E status, no beneficial effect of DFO was observed. The more lipophilic CP51 (25 mg/kg/24 h i.v.…”

Survival predictors in paraquat intoxification and role of immunosuppression

“…As acute renal failure of paraquat poisoning is presumably an oxidative stress disorder [15] , desferrioxamine may be useful in its treatment. In oxidative stress, lipid peroxidation may be enhanced by iron radicals, and chelating agent desferrioxamine has been shown to reduce toxicity in animal model [16] . Desferrioxamine was used in the management of a single patient with severe paraquat intoxication, in combination with decontamination, haemodialysis, and N acetylcysteine with good outcome [17] .…”

Os riscos e danos nas intoxicações por paraquat em animais domésticos

“…Nesse sentido, tem se enfatizado a utilização de algumas substâncias antioxidantes. Agentes que têm se mostrado benéficos em intoxicações por paraquat experimentais incluem nacetil-cisteína (HONORE et al, 1994), ácido ascórbico (HONG et al, 2002), á-tocoferol (BLOCK, 1979, superóxido dismutase, ácidos graxos monoinsaturados como o ácido oléico (FRITZ et al, 1994), betabloqueadores (PATEL & DAY, 1999), melatonina (MELCHIORRI et al, 1996), quelantes do ferro como desferroxamina e hidroxipiridin-4-ona ( VAN ASBECK et al, 1989; VAN DER WAL et al, 1990; VAN DER WAL et al, 1992), metalotioneína (SATOH et al, 1992), litoespermato (YOKOZAWA et al, 1998), corticosteróides (LIN et al,1996), talidomida, montelucaste e ácido acetil salicílico associados (CALDAS, 2004) e outras substâncias como o curcumin (VENKATESAN, 2000) e a 3-metil-1-fenil-2-pirazolin-5-ona (SAIBARA et al, 2003).…”