Prevention of thiourea-induced pulmonary edema by hydroxyl-radical scavengers. 1983

R B Fox, and R N Harada, and R M Tate, and J E Repine

Thiourea (TU), a very effective hydroxyl radical (.OH) scavenger, has little value as a probe of .OH in vivo because it causes fatal pulmonary edema. To test the hypothesis that TU-induced lung injury results from .OH-mediated oxidation of TU to toxic cyanamide, we pretreated rats with .OH scavengers, dimethylsulfoxide (DMSO), ethanol, and mannitol, prior to treatment with TU (3 mg/kg), preventing 91, 63, and 53%, respectively, of increases in lung weight to body weight ratios and 93, 67, and 46% of increases in lung lavage albumin concentrations. Furthermore, treatment of rats with cyanamide (CYN) (100 mg/kg) also caused increases in lung weight to body weight ratios (CYN: 7.39 +/- 0.57 X 10(-3) vs. controls: 5.46 +/- 0.26). N,N'-dimethylation of TU (DMTU) prevented TU toxicity, because treatment with DMTU did not significantly increase lung weight to body weight ratios (DMTU: 5.12 +/- 0.16 X 10(-3) vs. controls: 5.46 +/- 0.26) or lung lavage albumin (DMTU: 14 +/- 1 mg/100 ml vs. controls: 11 +/- 1). DMTU remained a very effective in vivo .OH scavenger, increasing survival of lethally irradiated mice treated with 600 mg/kg DMTU to 79% compared with 8% in untreated controls.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008353 Mannitol A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. (L)-Mannitol,Osmitrol,Osmofundin
D008697 Methane The simplest saturated hydrocarbon. It is a colorless, flammable gas, slightly soluble in water. It is one of the chief constituents of natural gas and is formed in the decomposition of organic matter. (Grant & Hackh's Chemical Dictionary, 5th ed)
D011654 Pulmonary Edema Excessive accumulation of extravascular fluid in the lung, an indication of a serious underlying disease or disorder. Pulmonary edema prevents efficient PULMONARY GAS EXCHANGE in the PULMONARY ALVEOLI, and can be life-threatening. Wet Lung,Edema, Pulmonary,Edemas, Pulmonary,Pulmonary Edemas,Lung, Wet,Lungs, Wet,Wet Lungs
D011833 Radiation Injuries, Experimental Experimentally produced harmful effects of ionizing or non-ionizing RADIATION in CHORDATA animals. Experimental Radiation Injuries,Injuries, Experimental Radiation,Experimental Radiation Injury,Radiation Injury, Experimental
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003484 Cyanamide A cyanide compound which has been used as a fertilizer, defoliant and in many manufacturing processes. It often occurs as the calcium salt, sometimes also referred to as cyanamide. The citrated calcium salt is used in the treatment of alcoholism. Calcium Carbimide,Calcium Cyanamide,Citrated Calcium Cyanamide,Abstem,Carbimide,Colme,Cyanamide, Calcium (1:1) Salt,Cyanamide, Calcium (2:1) Salt,Cyanamide, Calcium Salt,Temposil,Calcium Cyanamide, Citrated,Calcium Salt Cyanamide,Carbimide, Calcium,Cyanamide, Calcium,Cyanamide, Citrated Calcium
D004121 Dimethyl Sulfoxide A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation. DMSO,Dimethyl Sulphoxide,Dimethylsulfoxide,Dimethylsulphinyl,Dimethylsulphoxide,Dimexide,Rheumabene,Rimso,Rimso 100,Rimso-50,Sclerosol,Sulfinylbis(methane),Rimso 50,Rimso50,Sulfoxide, Dimethyl,Sulphoxide, Dimethyl
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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