Effects of diethyldithiocarbamate and nickel chloride on glutathione and trace metal concentrations in rat liver.
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 NiCl2 (0.25 or 0.50 mmol/kg, s.c.), singly or in combination. In rats treated with DDC or NiCl2, 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 NiCl2, hepatic GSH was not diminished at 4 h after increased 1.4-1.8-fold at 17 h. Hepatic GSSG was diminished at 4 h after NiCl2 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 NiCl2. Hepatic Ni was below the detection limit (approximately 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 NiCl2 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 NiCl2 or DDC, singly, and was not further increased by combined treatment; hepatic Cu and Mn concentrations were unaffected by NiCl2 or DDC, singly, but were diminished in rats that received NiCl2 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 NiCl2 and DDC; and (b) that increased hepatic uptake of Zn contributes to the induction of hepatic metallothionein by NiCl2 and DDC.
D000818:Animals; D003300:Copper / Q000032:analysis; D004050:Ditiocarb / Q000633:toxicity*; D004338:Drug Combinations; D004357:Drug Synergism; D005502:Food; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000032:analysis; D009532:Nickel / Q000032:analysis / Q000633:toxicity*; D011868:Radioisotopes; D051381:Rats; D011916:Rats, Inbred F344; D013859:Thiocarbamates / Q000633:toxicity*; D015032:Zinc / Q000032:analysis
D004338:Drug Combinations; D011868:Radioisotopes; D013859:Thiocarbamates; D008345:Manganese; D003300:Copper; D009532:Nickel; D004050:Ditiocarb; D005978:Glutathione; D015032:Zinc