Prevention of thiourea-induced pulmonary edema by hydroxyl-radical scavengers.
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.
D000818:Animals; D003484:Cyanamide / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D008168:Lung / Q000187:drug effects; D008353:Mannitol / Q000494:pharmacology; D008697:Methane / Q000096:biosynthesis; D011654:Pulmonary Edema / Q000139:chemically induced / Q000517:prevention & control*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000401:mortality; D051381:Rats; D011919:Rats, Inbred Strains; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology*
D000431:Ethanol; D008353:Mannitol; D003484:Cyanamide; C038983:1,3-dimethylthiourea; D013890:Thiourea; D008697:Methane; D004121:Dimethyl Sulfoxide