Plasma glutathione disulfide as an index of oxidant stress in vivo: effects of carbon tetrachloride, dimethylnitrosamine, nitrofurantoin, metronidazole, doxorubicin and diquat.

The plasma concentrations of glutathione and glutathione disulfide were measured in rats following the administration of diquat, metronidazole, nitrofurantoin, doxorubicin, dimethylnitrosamine or carbon tetrachloride. None of these agents significantly influenced the plasma concentrations of glutathione. Diquat, metronidazole and nitrofurantoin acutely increased plasma glutathione disulfide by 4 to 13 fold from 0.3 +/- 0.1 microM to 3.8 +/- 1.1 microM, 2.0 +/- 0.5 microM and 1.2 +/- 0.3 microM, respectively. Carbon tetrachloride, doxorubicin and dimethylnitrosamine did not affect plasma glutathione disulfide. The determination of plasma glutathione disulfide identifies compounds that generate potentially toxic amounts of reactive oxygen species during their metabolism and helps to distinguish these compounds from xenobiotics which generate organic free radicals and electrophilic metabolites under toxicologically relevant conditions.