thiourea and 1-1-3-3-tetramethylurea

The influence of four hydroxil radical (OH.) scavengers on platelet function was investigated. OH. scavengers inhibited ADP, collagen, arachidonic acid, PAF-induced platelet aggregation, and platelet cyclooxygenase pathway activation, which was studied by evaluating platelet malondialdehyde and serum thromboxane A2 formation. The latter was not affected by superoxide dismutase, catalase, or metal ion chelants such as desferioxamine or DETAPAC. The detection of deoxyribose degradation by stimulated platelets suggested that platelets produce OH.. This study shows that activated platelets produce free radicals and that antioxidant agents such as OH. scavengers inhibit platelet function.

Topics: Adult; Blood Platelets; Catalase; Chelating Agents; Dimethyl Sulfoxide; Ethylene Glycols; Female; Free Radicals; Humans; Hydroxides; Hydroxyl Radical; Male; Malondialdehyde; Methylurea Compounds; Platelet Aggregation Inhibitors; Platelet Function Tests; Prostaglandin-Endoperoxide Synthases; Superoxide Dismutase; Thiourea; Thromboxane B2

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