DIFFERENTIAL COMBINED EFFECT OF CADMIUM AND NICKEL ON HEPATIC AND RENAL GLUTATHIONE S-TRANSFERASES OF THE GUINEA-PIG

When male guinea pigs were given a single dose of Cd (2.0 mg Cd2+/kg, ip) 72 hr prior to sacrifice, the hepatic reduced glutathione (GSH) le vel did not change although glutathione S-transferase (GST) activities toward the substrates 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichlor o-4-nitrobenzene (DCNB), ethacrynic acid (EAA), and 1,2-epoxy-3-(p-nit rophenoxy) propane (ENPP) increased significantly as compared to contr ols. Cd did not change the renal GSH level and GST activities toward C DNB and EAA. However, significant increase was observed in the GST act ivity for DCNB whereas GST activity for ENPP was significantly inhibit ed by Cd. When the animals were given a single dose of Ni (14.8 mg Ni2 +/kg, sc) 16 hr prior to sacrifice, significant increases were observe d in hepatic GSH level and GST activities toward CDNB, DCNB, EAA and E NPP. Ni, however, depressed the renal GSH level and GST activities tow ard CDNB, DCNB and ENPP significantly. The renal GST activity toward E AA remained unaltered. For the combined treatment, guinea pigs receive d the single dose of Ni 56 hr after the single dose of Cd and then the y were killed 16 hr later. In these animals, no significant alteration was observed in the hepatic GSH level. The augmentation of elevation was observed in hepatic GST activities toward CDNB and DCNB. Combined metal treatment did not potentiate the elevation of hepatic GST activi ties toward EAA and ENPP to any greater degree. The depression of rena l GSH level was significantly ameliorated by the combined treatment. C ombination treatment potentiated the depression of renal GST activity for ENPP but not for CDNB. The renal GST activities toward DCNB and EA A, however, were unaltered by the combined metal treatment. These resu lts reveal that the hepatic and renal GSTs of the guinea pig are diffe rentially regulated by Cd or Ni alone and in combination, and that the combination of Cd and Ni does have an additive effect on hepatic and renal GSTs depending on the substrates of GSTs.