Diethyldithiocarbamate, superoxide dismutases

Cultured cells subjected to 0.8 mg/L for 3 h, recovery for 21 days 50% frequency of chromosomal aberrations higher frequency by pretreatment with diethyldithiocarbamate (an inhibitor of superoxide dismutase), or dimethyl maleate (a glutathione scavenger), or at high oxygen concentrations (Sofuni and Ishidate 1988)... 

Nalbandyan, 1982 Hodgson and Fridovich, 1975 Asada et al., 1975), whereas azide inhibits the enzymes in the following order iron > manganese > copper/zinc superoxide dismutase (Misra and Fridovich, 1978). Diethyldithiocarbamate is another well-characterized inhibitor of the copper/zinc superoxide dismutase (Heikkila et al., 1977). It forms a complex with the copper and removes the metal from all the protein ligands. The copper-diethyldithiocarbamate complex can be separated without affecting the zinc content of the protein (Cocco et al., 1981). 

Neuronal loss was initiated by inhibition of the antioxidant enzyme, superoxide dismntase (EC 1.15.1.1.) type 1, using the copper chelator diethyl-dithiocarbamate (Moskowitz et al. 2001). Continuous diethyldithiocarbamate treatment of Sprague-Dawley rat or C57/B16 mouse hippocampal slice cultures induced delayed neuronal loss beginning at 9 days of treatment that lasted for over 4 weeks. Neuronal loss was significantly attenuated in slice cultures that overexpress superoxide dismutase type 1, suggesting that superoxide dismutase inhibition was responsible. Inhibitors of nitric oxide synthase also attenuated diethyldithiocarbamate-induced neuronal loss. 

Sohal, R. S., Farmer, K. J., Allen, R. G., and Ragland, S. S., 1984, Effects of diethyldithiocarbamate on lifespan, metabolic rate, superoxide dismutase, catalase, inorganic peroxides and glutathione in the adult male housefly, Musca domestica, Mech. Aging Dev. 24 175-183. 

Diethyldithiocarbamate has long been used as an inhibitor of copper—zinc superoxide dismutase (SOD) (1780,1781). The SOD-Uke activity of bis(dithio-carbamate) complexes derived from amino acids has been determined, with glutamine dithiocarbamate showing high activity (131). Warshawsky et al. (1676) also prepared and assessed a range of dithiocarbamates with ohgoether chains (Fig. 238), which leads to >1000-fold increase in hydrophobicity versus diethyldithiocarbamate, with only a 2.3-fold decrease in SOD-like activity. 

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