thiourea and 1-1-dimethylurea

Dimethylthiourea (DMTU) is a small, highly diffusible molecule that effectively scavenges toxic oxygen metabolites in vitro and reduces oxidative injury in many biologic systems. Nonetheless, for unknown reasons, DMTU has occasionally failed to decrease damage in some systems where injury is presumed to be mediated by oxygen metabolites. We hypothesized that the inconsistent pattern of protection might partially reflect a direct toxicity of DMTU. Our results supported this premise. We found that rats treated with commonly used doses of highly purified DMTU had increased lung accumulation of intravenously injected iodine 125-labeled albumin (4 hours after DMTU treatment) and decreased blood glutathione levels (24 hours after DMTU treatment) when compared with saline-injected control rats. In contrast, rats treated with dimethylurea, a analog of DMTU, did not develop increased accumulation of labeled albumin in the lungs or decreased blood glutathione levels. We conclude that DMTU has intrinsically toxic effects in rats and that DMTU toxicity may at times obscure its protective action.

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Glutathione; Lung; Male; Methylurea Compounds; Organ Size; Rats; Rats, Sprague-Dawley; Serum Albumin; Stomach; Thiourea

Eugenol, an extract of cloves, has been associated with pulmonary edema when inhaled from commercially available clove cigarettes. We tested the hypothesis that eugenol directly causes lung edema through oxidant-mediated mechanisms by infusing eugenol (0.1 and 1.0 mM) into isolated rabbit lungs perfused with a cell-free albumin and physiologic salt solution. We observed lung edema (1.0 mM) as demonstrated by increased lung weight gain and wet-to-dry lung weight ratios without alterations in mean pulmonary artery pressure. The oxygen metabolite scavengers catalase (1,000 U/ml) and dimethylthiourea (30 mM) attenuated lung edema. Instillation of dimethylurea, superoxide dismutase, or heat-inactivated catalase did not prevent lung edema formation. We conclude that eugenol causes lung edema in isolated lungs through oxidant-mediated mechanisms in the absence of circulating formed blood elements. Eugenol may be a valuable compound in the laboratory investigation of edemogenic disorders.

Topics: Animals; Blood Pressure; Catalase; Eugenol; In Vitro Techniques; Lung; Methylurea Compounds; Organ Size; Oxygen; Pulmonary Artery; Pulmonary Edema; Rabbits; Superoxide Dismutase; Thiourea

Agents that are known to be scavengers of hydroxyl radicals inhibit lymphocyte mitogenesis induced by phorbol myristate acetate (PMA) to a greater extent than they inhibit mitogenesis induced by concanavalin A or phytohemagglutinin. These agents include dimethyl sulfoxide, benzoate, thiourea, dimethylurea, tetramethylurea, L-tryptophan, mannitol, and several other alcohols. Their inhibitory effect is not associated with cytotoxicity. The hydroxyl radical scavengers do not inhibit PMA-dependent amino acid transport in T cells or PMA-induced superoxide production by monocytes. Thus, they do not inhibit the primary interaction of PMA with responding cells. Treatment of peripheral blood mononuclear cells with PMA increased cellular guanylate cyclase in most experiments, and dimethyl sulfoxide tended to inhibit this increase. In addition to inhibition of PMA-induced mitogenesis, hydroxyl radical scavengers markedly inhibited the activity of lymphocyte activating factor (interleukin 1). The differential inhibition of lymphocyte mitogenesis induced by different mitogens appears to be related to the differential macrophage requirements of the mitogens. The data suggest that hydroxyl radicals may be involved in mediating the triggering signal for lymphocyte activation. Some of the hydroxyl radical scavengers are inducers of cellular differentiation,. nd it is possible that their differentiating activity is related to their ability to scavenge free radicals.

Topics: Benzoates; Benzoic Acid; Concanavalin A; Dimethyl Sulfoxide; Free Radicals; Guanylate Cyclase; Humans; Lymphocyte Activation; Lymphocytes; Macrophages; Mannitol; Methylurea Compounds; Phytohemagglutinins; Tetradecanoylphorbol Acetate; Thiourea

Isopiestic equilibration measurements were made on ten protein-denaturant systems involving polyglycine, egg albumin, collagen, horse heart myoglobin, and the denaturants urea, 1,3-dimethylurea, 1,1-dimethylurea, and thiourea. The hydration of the proteins in the absence of denaturants is a function of the water activity and it is believed that this accounts, at least in part, for the varying hydration values found in the literature. The relative binding of water and denaturant to unfolded proteins was found to be a reversible process for which an equilibrium constant can be calculated. It was further found that in most cases the protein binds denaturant preferentially to water even in aqueous systems.

Topics: Glycine; Methylurea Compounds; Peptides; Protein Denaturation; Proteins; Thiourea; Urea