Disease relevance of Diethyldithiocarbamic acid

• Reduction of new opportunistic infections in the ditiocarb group was significant in all patients (relative risk [RR], 0.44) and in patients with AIDS (CDC groups IV-C1 and IV-D) (RR, 0.12) [1].
• The disease did not progress to CDC-defined acquired immunodeficiency syndrome in the ditiocarb group but did so in 4 patients in the placebo group (3 between week 0 and 16, 1 between week 17 and 32) [2].
• 60 patients with HIV-1 infection in Walter Reed stages 2-4 were randomised to treatment with intravenous or oral dithiocarb (diethyldithiocarbamate, DTC) or placebo for 24 weeks in a paired double-blind design [3].
• Ditiocarb was also associated to a significantly greater extent than placebo with relief of constitutional symptoms, improvement in clinical status (including shrinkage of enlarged spleen and lymph nodes), and improvement in immune function (as measured by CD4+ cell count and skin test reactivity) [2].
• 83 patients with human immunodeficiency virus (HIV) infection (CDC groups II, III, or IV-A) were randomised in a crossover trial of sodium-diethyldithiocarbamate (ditiocarb sodium, 'Imuthiol') (10 mg/kg body weight given orally once a week) against placebo [2].

High impact information on Diethyldithiocarbamic acid

• Neonatal rat ventricular myocytes in vitro were exposed to diethyldithiocarbamic acid (DDC), an inhibitor of cytosolic (Cu, Zn) and extracellular superoxide dismutase (SOD) [4].
• Isoprinosine and Imuthiol are immunomodulators with a unique effect on T-cells [5].
• Isoprinosine and Imuthiol, two potentially active compounds in patients with AIDS-related complex symptoms [5].
• Isoprinosine and Imuthiol increased significantly both the percentage and the absolute number of T4+ cells when peripheral blood mononuclear cells were incubated for 4 days in RPMI supplemented with 10% fetal calf serum [5].
• In the presence of neutrophils, the A1242-induced luminol chemiluminescence was decreased by the superoxide dismutase inhibitor diethyldithiocarbamic acid (DDC) and the myeloperoxidase inhibitor salicylhydroxamic acid (SHA) [6].

Chemical compound and disease context of Diethyldithiocarbamic acid

• Administration of the aldehyde dehydrogenase inhibitor diethyldithiocarbamic acid had little effect on the conversion of NPOH to NPA and did not alter the toxicity of NPOH [7].
• In in vivo experiments, inhibition of SOD by diethyldithiocarbamic acid (0.5 mg. kg(-1). min(-1) iv) enhanced renal vasoconstriction induced by endogenously produced adenosine and increased renal tissue adenosine concentrations under control condition and in ischemia and reperfusion [8].
• CYP 2E1 activities detected by 4-nitrocatechol (4-NC) formation were higher in gel entrapped hepatocytes than in hepatocyte monolayers while the addition of CYP 2E1 inhibitor, diethyl-dithiocarbamate (DDC), more significantly reduced acetaminophen-induced toxicity in gel entrapped hepatocytes [9].

Biological context of Diethyldithiocarbamic acid

• Microglia activation and cell death in response to diethyl-dithiocarbamate acute administration [10].
• In contrast, prolonged (24 h) exposure to the copper-zinc superoxide dismutase inhibitor diethyldithiocarbamic acid (DDC, 1 microM) similarly augmented oxyradicals but also increased cell size, and contraction and Ca2+ transient duration (P<0.025) [11].
• A third compound, diethyldithiocarbamic acid (DETC), incubated for 1-7 days, produced a significant dose response suppression of cell growth of DU-145 and ALVA-101 cells (P < 0.01; 14-88% of control; 1.25-80 microg/ml; n = 6) [12].
• Inhibition of mixed-function oxidases by dithiocarb did not prevent the decrease in oxygen consumption and the resulting hepatic injury induced by paracetamol [13].
• After treatment with DETCA, duroquinone produced greater reductions of relaxant responses to NO and to nitrergic stimulation, the IC50 values being 8.5 microM for NO and 40 microM for nitrergic nerve stimulation: these reductions were reversed by SOD [14].

Anatomical context of Diethyldithiocarbamic acid

• It is concluded that Imuthiol may affect immune responsiveness by acting directly on the neocortex and/or by interacting at subcortical levels with signals emitted by the neocortex [15].
• In contrast, diethyldithiocarbamic acid, an inhibitor of superoxide dismutase, or Tiron, a scavenger of superoxide anion, reduced endothelium-dependent contractions to acetylcholine in aortas from SHR [16].
• Imuthiol inhibits the etoposide-induced apoptosis in HL-60 cells [17].
• Favorable influences of imuthiol on mouse reproduction and immune system of offspring [18].
• The data suggest that imuthiol has no teratogenicity or deleterious influences on mouse gametes, and might be useful to prevent immunodepression-associated infections in newborns [18].

Associations of Diethyldithiocarbamic acid with other chemical compounds

• Reduction in cell death and increase in oxygen radicals with BW373U86 were blocked by the selective mitochondrial KATP channel antagonist 5-hydroxydecanoate or diethyldithiocarbamic acid (1,000 microM), which inhibited conversion of O2- to H2O2 [19].
• We have recently shown that dithiocarbamate (DC) disulfides inhibit proteolytic processing of the caspase-3 proenzyme in Jurkat T lymphocytes treated with anti-CD95 (Fas/APO-1) antibody [20].
• Tritrichomonas foetus was also sensitive-the MICs for seven metronidazole-sensitive isolates were 0.1-1.0 microM for disulfiram and 1.0-6.9 microM for ditiocarb; those for two highly metronidazole-resistant strains were 0.3-1.3 microM and 0.6-6 microM respectively [21].
• The glutathione peroxidase ebselen (converting H(2)O(2) to H(2)O) and the superoxide dismutase inhibitor diethyldithiocarbamic acid abolished the increased H(2)O(2) and the protection of preconditioning [22].
• Sodium diethyldithiocarbamate ( imuthiol ), a non-antigenic and non-carcinogenic compound, devoid of toxic effects at immunostimulant doses, shows distinctive properties in recruitment and activation of T cells [23].

Gene context of Diethyldithiocarbamic acid

• Superoxide dismutase (SOD) with catalase produced a concentration-dependent reduction of 5'-ND activity in renal tissue homogenate, while the SOD inhibitor diethyldithiocarbamic acid significantly increased 5'-ND activity [8].
• On the other hand, MAO-A activities were decreased gradually with an increasing concentration of o-phenanthroline and diethyldithiocarbamic acid, but these metal chelators had no effect on MAO-B activity in monkey brain [24].
• The protective role of antioxidant enzymes against NO-induced oxidative damage in U937 cells was investigated in control and cells pre-treated with diethyldithiocarbamic acid, aminotriazole, and oxlalomalate, specific inhibitors of superoxide dismutase, catalase, and NADP(+)-dependent isocitrate dehydrogenase, respectively [25].
• The Cu/Zn SOD inhibitor, diethyldithiocarbamic acid (DETCA; 8 mM), inhibited the relaxation of intact and denuded mucosa stomach fundus to UV light irradiation, EFS, NO and nitroglycerin but not those to isoproterenol [26].
• The same dose of Imuthiol also stimulated IL2 production by human PBL [27].

Analytical, diagnostic and therapeutic context of Diethyldithiocarbamic acid

• A high-performance liquid chromatography (HPLC) method is described for the determination of reactive nitrogen mustard anticancer drugs in plasma after derivatization with diethyl-dithiocarbamic acid (DDTC) [28].
• Saline or NF-kappaB inhibitor diethyldithiocarbamic acid (DDTC, 50, 100 or 200 mg kg(-1)) was given intravenously 5 min prior to reperfusion [29].
• Influenza vaccination in the elderly: improved antibody response with Imuthiol (Na diethyldithiocarbamate) adjuvant therapy [30].
• Sodium diethyldithiocarbamate (Imuthiol, DTC) has previously been observed to promote T-cell maturation in animal models and to reduce lymphadenopathy and improve survival in a murine AIDS model [31].
• Consequences of bilateral brain neocortical ablation on imuthiol-induced immunostimulation in mice [32].

References