The effect of diethyldithicarbarnate on antioxidant enzyme activities in the blood of rats

Diethyldithiocarbamate (DDC) exhibits a variety of effects including neurotoxic, radio-protective and sensitizing activity. It is a potent copper chelating agent used for the treatment of oxygen toxicity, as an imunomodulator in cancer therapy, as well as in HIV infected patients. In this study we examined the effect of DDC, a superoxide dismutase (SOD) inhibitor, on the activities of copper-zinc containing superoxide dismutase (CuZn SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST). Three hours after diethyldithiocar-bamate treatment (1 g/kg b.m, i.p) a significant decrease of SOD and increase of GR and GST activities were found in the blood of rats. A negative correlation between SOD and GR and a positive correlation between GR and GST activities were also obtained. DDC induced a concentration dependent increase of GR activity and NADPH consumption in an enzymatic assay in vitro. The obtained results may be interpreted to indicate that a decrease in SOD activity in the blood of rats, after DDC administration, may be compensated for by changes in the activity of some other compounds suggesting that regulation of antioxidative defence is very complex.Dietilditiokarbamat (DDC) ispoljava različite uticaje kao što su neurotoksičnost, radioprotekcija i senzibilizacja. On je snažan helirajući agens za bakar i koristi se u tretiranju kiseonične toksičnosti imunomodulaciji kao i kod pacijenata zaraženih HIV virusom. U ovom radu smo proučavali uticaj DDC, inhibitora superoksid dismutaze (SOD), na aktivnost bakar cink sadržavajuće superoksid dismutaze (CuZn SOD), katalaze (CAT) glutation peroksidaze (GSH-Px), glutation reduktaze (GR) i glutation-S-transferaze (GST).Tretiranje pacova dietilditiokarbamatom u trajanju od tri časa (1g/kgt.m, i.p) dovodi do značajnogsmanjenja aktivnosti CuZn SOD i povećanja aktivnosti GR i GST u krvi pacova. Takodje je dobijena negativna korelacija izmedju SOD i GR aktivnosti. DDC indukuje povećanje GR aktivnosti koje je koncentraciono zavisno kao i NADPH potrošnju u in vitro enzimatskom eseju. Dobijeni rezultati ukazuju na činjenicu da smanjivanje aktivnosti SOD u krvi pacova posle tretiranja DDCom može biti kompenzovano promenom aktivnosti drugih komponenti što dalje sugeriše da je regulacija antioksidacione zaštite veoma kompleksna.nul