Diethyldithiocarbamate (ditiocarb sodium) effect on arachidonic acid metabolism in human mononuclear cells. Glutathione peroxidase-like activity.

摘要: Diethyldithiocarbamate (DTC), a thiol delivery agent, has been shown to significantly reduce the frequency of primary opportunistic infections in HIV-infected patients. This therapeutic effect related capacity DTC reverse deleterious effects oxidative stress occurring HIV infection. The influence on oxygenated metabolism arachidonic acid (AA) was investigated mitogen-stimulated human peripheral blood mononuclear cells (PBMC). Upon incubation with PBMC previously labelled [3H]AA, Concanavalin A (Con A) markedly increased cyclooxygenase and lipoxygenase activities, within 30 min, as judged by thromboxane B2 (TxB2) hydroxyeicosatetraenoic (HETE) production. Con activation [3H]AA platelets also 12-HETE production but did not induce any TxB2 synthesis. Micromolar concentrations DTC, added simultaneously mitogen, enhanced synthesis HETEs above A-induced level while TxB2-induced inhibited only at higher than 50 microM. In presence nordihydroguaiaretic acid, inhibitor, which 78%, no longer stimulated HETE level. Reverse phase HPLC analysis showed that 5-, 12- 15-HETEs. 5 microM 5-HETE entirely suppressed whereas 15-HETE enhanced, contaminating remained unchanged. vitro experiments indicated alone 15-hydroperoxyeicosatetraenoic (15-HPETE) soybean 15-lipoxygenase but, reduced glutathione, 15-HPETE into 15-HETE. addition, able substitute for cellular extract glutathione peroxidase (GPx) assay system. Taken together, these results indicate through its "GPx-like" activity is modify cascade. Its ability selectively known stimulate immunosuppressive T-cells might help explain positive regulatory upon immune