The effects of sodium diethyldithiocarbamate in fibroblasts V79 cells in relation to cytotoxicity, antioxidative enzymes, glutathione, and apoptosis

Abstract

Sodium diethyldithiocarbamate (DETC) is the main metabolite of disulfiram. Recently, we reported that mechanism of disulfiram cytotoxicity in V79 cells might be partially connected with thiol redox-state imbalance. Here, we examined the effect of DETC on the level of intracellular glutathione (GSH), protein oxidation (measured as PC—protein carbonyl content), lipid peroxidation (measured as TBARS—thiobarbituric acid reactive substances), antioxidant enzymatic defense, as well as on apoptosis. We used V79 Chinese hamster fibroblasts cells with and without modulated glutathione (GSH) level by N-acetyl-l-cysteine (NAC). We showed that treatment with DETC at concentrations that cause a moderate increase in thiol-state imbalance but not cell death stimulates oxidative stress measured as increased level of PC and TBARS, adaptive response of GSH-related enzymes and apoptosis. Our results show that cellular effects of DETC are partially attributable to the initial redox cellular state, since the increase of GSH level by NAC pre-treatment prevented the observed changes.

Brain zinc chelation by diethyldithiocarbamate increased the behavioral and mitochondrial damages in zebrafish subjected to hypoxia

“…This fact suggests that even attenuating the increased content of chelatable Zn, DEDTC probably played a pro-oxidant effect. In accordance with this data, Rahden-Staroń et al 12 have shown that the administration of DEDTC on cell culture generates oxidative damage in proteins and lipids along with the induction of antioxidant enzymes and production of glutathione. In fact, we verified that DEDTC per se promoted a significant increase of sulfhydryl content as a probable response to toxic mechanisms, since we observed mitochondrial damage and exploratory deficit in these same animals.…”

“…Due to Zn-binding properties, it has been suggested that DEDTC may play a neuroprotective role against hypoxia. However, the application of DEDTC as protective drug must be thoroughly investigated, since it is a redox-active compound that may impair cellular antioxidant/oxidant homeostasis 11 12 .…”

Sulfasalazine inhibits inflammation and fibrogenesis in pancreas via NF-κB signaling pathway in rats with oxidative stress-induced pancreatic injury

“… 16 In our present study, rats were treated with DDC, a reagent which could incite oxidative stress and lead to cell damage. 17 As a result, inflammation, acinar atrophy, and fibrogenesis were observed inside the pancreatic tissues after DDC administration, suggesting development of oxidative stress-induced pancreatic injuries. In consideration of the role of oxidative stress in development of pancreatic injury, antioxidant is believed to be an effective therapy.…”

Disulfiram partially improves oxidative but not androgen status in rats exposed to cadmium

“…Cd affects both antioxidant enzymes. It binds to their -SH groups, displacing metals (cofactors) from their active sites, altering the secondary structure of CAT and SOD, which leads to enzyme misfolding and prevention of the access of substrate to the active site of the enzyme, thus reducing or inactivating their enzymatic activities [26][27][28][29].…”