Failure of desferrioxamine to modify the toxicity of paraquat in rats
The feasibility of using desferrioxamine (DF), an iron chelator, as a therapeutic agent against paraquat (PQ/sup + +/) toxicity in male Sprague-Dawley rats was explored, based on the rationale of limiting toxic hydroxyl radical production from hydrogen peroxide by removing redox-active iron. Body weights, mortality, and lung histopathology were followed for periods up to 14 days after intraperitoneal injection of PQ/sup + +/ (20 or 25 mg/kg body weight) with or without concurrent daily subcutaneous injections of DF (300 mg/day). Animals receiving PQ/sup + +/ showed the expected typical patterns of mortality and of lung histopathology, namely: marked edema, subpleural hemorrhage, acute inflammation, perivascular mononuclear cell infiltrates, sloughing of alveolar and bronchiolar lining cells, and diffuse interstitial fibrosis. Desferrioxamine alone was non-toxic. Surprisingly, results when both PQ/sup + +/ and DF were administered indicated a failure of DF to ameliorate toxic effects of PQ/sup + +/ in the lung, and even suggested an accentuation of PQ/sup + +/-induced damage by DF. Mortality data showed that PQ/sup + +//DF animals died in greater numbers (20 mg PQ/sup + +//kg) or died earlier (25 mg PQ/sup + +//kg) than animals receiving DF alone. Qualitative histopathology in PQ/sup + +//DF animals was comparable to PQ/sup + +/ animals in early stages, but damage was more severe in both incidence and severity of lesions in PQ/sup + +//DF animals, particularly at the 25 mg PQ/sup + +//kg dose level. After 14 days, surviving animals receiving PQ/sup + +/ alone showed almost complete resolution of previous inflammation and other acute effects, whereas in the only surviving PQ/sup + +//DF animal initial fibrosis had persisted and become more generalized. 51 references, 6 figures, 2 tables.
- Research Organization:
- Brookhaven National Lab., Upton, NY
- DOE Contract Number:
- AC02-76CH00016
- OSTI ID:
- 6133494
- Journal Information:
- J. Free Radi. Biol. Medic.; (United States), Vol. 1
- Country of Publication:
- United States
- Language:
- English
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CHELATING AGENTS
BIOLOGICAL EFFECTS
HERBICIDES
TOXICITY
LUNGS
PATHOLOGICAL CHANGES
EXPERIMENTAL DATA
IRON
MORTALITY
RATS
WEIGHT
ANIMALS
BODY
DATA
ELEMENTS
INFORMATION
MAMMALS
METALS
NUMERICAL DATA
ORGANS
PESTICIDES
RESPIRATORY SYSTEM
RODENTS
TRANSITION ELEMENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)