Dichloroacetate-induced modulation of cellular antioxidant enzyme activities and glutathione level in the J774A.1 cells.
Dichloroacetate (DCA) is used for different medical and industrial purposes and has been found to be a toxic by-product produced during the process of water chlorination. The DCA effects on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities and glutathione (GSH) level were assessed and correlated with each other and also with cellular viabilities in J774A.1 macrophage cells. A concentration of 24 mm of DCA resulted in time-dependent decreases in cellular viability and glutathione level, and time-dependent increases in SOD activity when incubated with the cells for 24-48 h. DCA also resulted in significant increases in CAT and GSH-Px activities of the viable cells when incubated with the cells for 36 and 48 h. The changes in antioxidant enzyme activities and GSH levels were found to be strongly correlated with each other, and with cellular viabilities at different time points. While GSH did not result in any significant effects when added to the cells at concentrations ranging between 15 and 60 nmol ml(-1), it resulted in concentration-dependent increases in cellular viability when added to the DCA-treated cells, with maximal effects achieved at 45-60 nmol GSH ml(-1). However, cellular viability of the GSH + DCA treated cells remained below that of the control. Since viable cells from the DCA-treated cultures displayed significantly higher antioxidant enzyme activities compared with the control, it is concluded that those increases may have contributed to the cellular protection against DCA-induced cell death. Also, glutathione depletion has a major contribution to the observed cellular death induced by DCA.
Hassoun
Ezdihar A
EA
The University of Toledo, College of Pharmacy, Toledo, OH 43606, USA. ezdihar.hassoun@utoledo.edu
Mehta
Jatin
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007202:Indicators and Reagents; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D010586:Phagocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D007202:Indicators and Reagents; D003999:Dichloroacetic Acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione