title: Dimethylthiourea consumption reflects H2O2 concentrations and severity of acute lung injury.
abstract: Even though dimethylthiourea (DMTU) effectively scavenges O2 metabolites in vitro, it is often unclear if scavenging of O2 metabolites is the mechanism by which DMTU decreases tissue injury in biological models. Since DMTU not only scavenges O2 metabolites but is also consumed in a dose-response manner following reaction with hydrogen peroxide (H2O2) in vitro, we wondered whether DMTU would also be consumed by O2 metabolites in biological systems and if DMTU consumption would then reflect O2 metabolite concentrations and O2 metabolite-mediated injury. Our results supported this possibility. We found that selected nonprotecting concentrations of DMTU were consumed in isolated rat lungs perfused with H2O2 and that the amounts of DMTU consumed reflected both the added amounts of H2O2 and the corresponding degrees of H2O2-induced acute edematous injury. DMTU consumption was relatively specific for reaction with H2O2 occurring in isolated lungs that were injured by H2O2 but not lungs injured by elastase, oleic acid, histamine, or a venous pressure challenge. Our results suggest that measurement of DMTU consumption may be useful for assessing the presence and toxicity of O2 metabolites and the specificity of the protective effects of DMTU in biological systems.
mesh_terms: D000818:Animals; D002268:Carboxypeptidases / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011654:Pulmonary Edema / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013890:Thiourea / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: C038983:1,3-dimethylthiourea; D006861:Hydrogen Peroxide; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; D013890:Thiourea