Hepatic and renal metallothionein induction by an oral equimolar dose of zinc, cadmium or mercury in mice.
The hepatic and the renal subcellular distribution of zinc, cadmium or mercury and induction of tissue metallothionein (MT) at 24, 48 and 72 h following an oral equimolar dose (15 micro;mol metal/kg) of zinc (II) chloride, cadmium (II) chloride or mercury (II) chloride in male albino mice were investigated. There was a moderate increase in hepatic and renal zinc levels mainly in their nuclear mitochondrial fraction (NMF) 24 h post zinc chloride administration. Subsequently, the hepatic zinc increased and the renal zinc declined with time. The zinc-induced hepatic MT level was maximum at 48 h, which decreased slightly thereafter, while there was no marked increase in renal MT level at any time interval. The cadmium was equally distributed in liver and kidney more in their supernatant cytosol fraction (SCF) than in their NMF at 24 h after a dose of cadmium chloride. The cadmium levels showed a decreasing trend in hepatic fractions and an increasing trend in renal fractions with time. The cadmium-induced hepatic and renal MT were substantial at 24 h post cadmium administration, the former decreased thereafter while the latter enhanced at 48 h before declining. The accumulation of mercury in kidney was 1.5 times that in liver, which was localised more in their SCF than in their NMF at 24 h in response to a dose of mercuric chloride. The mercury levels of hepatic and renal subcellular fractions started declining after 24 h and at 72 h they were significantly lower. The induction of hepatic and renal MT was maximum at 24 h after mercuric chloride administration, which declined thereafter concomitant with the decrease in their mercury levels. However, the MT levels in both the organs remained considerably higher than in normal animals at 72 h post exposure. The results show that the accumulation of metal in liver and kidney follows the order: Hg > Cd > Zn and the induction of MT follows Hg > Cd > Zn in liver and Cd > Hg > Zn in kidney. The alterations in zinc and copper homeostasis were more marked in liver than in kidney and follows the order: Hg > Cd > Zn.
Tandon
S K
SK
Chemical Toxicology, Industrial Toxicology Research Centre, P0 Box 80, -226001, Lucknow, India. intox@itrc.sernetd.ernet.in
Singh
S
S
Prasad
S
S
Mathur
N
N
D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006706:Homeostasis; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008628:Mercury / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008657:Metabolic Clearance Rate; D008668:Metallothionein / Q000096:biosynthesis / Q000187:drug effects*; D051379:Mice; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D013997:Time Factors; D015032:Zinc / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D017967:Zinc Compounds / Q000008:administration & dosage / Q000494:pharmacology
D002712:Chlorides; D017967:Zinc Compounds; D002104:Cadmium; C016837:zinc chloride; D008668:Metallothionein; D008628:Mercury; D015032:Zinc; D019256:Cadmium Chloride