Effects of diethyldithiocarbamate and nickel chloride on glutathione and trace metal concentrations in rat liver

Abstract

Concentrations of reduced glutathione (GSH) and oxidized glutathione (GSSG) and 4 trace metals (Ni, Cu, Mn, Zn) were measured in livers from rats treated with sodium diethyldithiocarbamate (DDC, 0.67 or 1.33 mmol/ kg, i.m.) and NiCl 2 (0.25 or 0.50 mmol/kg, s.c.), singly or in combination. In rats treated with DDC or NiCl 2, singly, hepatic GSH was diminished at 4 h and returned to control levels (or slightly above) at 17 h. In rats that received DDC plus NiCl 2, hepatic GSH was not diminished at 4 h and was increased 1.4–1.8-fold at 17 h. Hepatic GSSG was diminished at 4 h after NiCl 2 treatment and returned to control values at 17 h; hepatic GSSG did not differ from control values at 4 h or 17 h after treatment with DDC, alone or combined with NiCl 2. Hepatic Ni was below the detection limit (∼ 20 nmol/g) in control and DDC-treated rats; hepatic Ni was increased to 53 ± 26 (S.D.) nmol/g at 17 h after treatment with NiCl 2 alone, and was increased 6-fold (308 ± 63 nmol/g in rats that received Ni plus DDC. Under the same conditions, hepatic Zn was increased 33% or 41%, respectively, in rats that received NiCl 2 or DDC, singly, and was not further increased by combined treatment; hepatic Cu and Mn concentrations were unaffected by NiCl 2 or DDC, singly, but were diminished in rats that received NiCl 2 and DDC. This study suggests: (a) that increased hepatic uptake of Ni is largely responsible for the synergistic induction of heme oxygenase activity in rats treated with NiCl 2 and DDC; and (b) that increased hepatic uptake of Zn contributes to the induction of hepatic metallothionein by NiCl 2 and DDC.