Protective roles of metallothionein and glutathione in hepatotoxicity of cadmium.
The protective roles of metallothionein (MT) and glutathione (GSH) in acute hepatotoxicity of cadmium (Cd) were investigated in an in vitro system. Liver slices were incubated in a buffer containing cadmium chloride (20-50 ppm) at 37 degrees C for 3 h. Viability of the slices was monitored by measuring intra-cellular potassium (K) content and GSH concentrations. A dose-dependent decrease of intracellular K content of GSH concentrations was observed. Pre-induction of MT (100-fold increase) by injection of zinc sulphate (30 mg Zn/kg body weight) showed protection against decrease in both intracellular K and GSH concentrations in liver slices. Decrease of hepatic GSH (90%) by an injection of buthionine sulfoximine (BSO)(4 mmol/kg body weight) to the rats further enhanced the Cd toxicity in the liver slices. This enhanced toxicity resulting from BSO treatment can be totally overvome by induction of MT by Zn pre-treatment. The cellular uptake of Cd remained unaltered in all experiments. These results demonstrate that hepatic toxicity of Cd may be due to its binding to intracellular sulfhydryl groups and both intracellular GSH and MT levels may provide protection against cytotoxicity of Cd in liver. Moreover, even at low GSH levels, MT could partially protect the hepatic cells from Cd cytotoxicity.
Chan
H M
HM
Department of Pathology, University of Western Ontario, London, Canada.
Cherian
M G
MG
D000818:Animals; D019328:Buthionine Sulfoximine; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004347:Drug Interactions; D004790:Enzyme Induction; D005978:Glutathione / Q000502:physiology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis / Q000502:physiology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology; D019287:Zinc Sulfate
D013431:Sulfates; D002104:Cadmium; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D019287:Zinc Sulfate; D008668:Metallothionein; D005978:Glutathione; D015032:Zinc