Influence of chelating agents on toxicity and distribution of cadmium among proteins of mouse liver and kidney following oral or subcutaneous exposure.
Acute toxicity and organ distribution of cadmium was investigated in mice exposed to 1) single subcutaneous doses of 109Cd-labelled cadmium (3.2 mg (0.028 mmol)/kg b.wt.) alone or in combination with nitrilotriacetic acid, NTA (32 mg (0.167 mmol/kg b.wt.) or sodium tripolyphosphate, STPP (32 mg (0.087 mmol/kg b.wt.) and 2) single oral doses of cadmium (60 mg (0.53 mmol/kg b.wt.) alone or together with NTA (600 mg (3.14 mmol)/kg.b.wt.) or STPP (600 mg (1.63 mmol/kg b.wt.) Whole-body retention of radiolabelled cadmium as well as mortality was registered in all groups during 20-21 days. Five hours after exposure, 3-4 mice in each group were killed and cadmium distribution among proteins in liver and kidney studied by gel chromatography on a G-75 Sephadex column. Organ concentration of cadmium was also determined at sacrifice of all other mice after an observation time of 20-21 days. A markedly increased mortality was observed during the first 24 hours after subcutaneous exposure to Cd + NTA (70%) or Cd + STPP (40%) compared to Cd alone (0%). On the contrary, no mortality was seen after oral exposure to Cd + NTA (70%) or CD + STPP (while oral exposure to Cd alone or with NTA resulted in a mortality of about 45% during the same observation time. Five hours after subcutaneous exposure, liver cadmium concentrations were equal in all mice and bound mainly to a low molecular weight protein (probably metallothionein). In kidney, concentrations were about twice as high in mice given Cd + NTA or CD + STPP compared to mice given Cd alone. More cadmium was transferred to the kidneys in the presence of chelating agents. This was further supported by the decreased liver/kidney cadmium concentration ratio between 5 hours and 21 days. The increased mortality in mice given Cd + NTA or Cd + STPP may be due to an initially high accumulation of cadmium in liver, which may exceed the upper limit for metallothionein synthesis, whereby toxic damage of the hepatic cells and leakage of cadmium from the liver would occur. Five hours after oral exposure, cadmium retention in organs of mice given Cd + STPP was 4-6 times lower than in mice given Cd alone, while mice given Cd + NTA had slightly higher organ concentrations. The binding of more cadmium to metallothionein in liver of Cd + STPP-exposed mice 5 hours after exposure, may be due to the lower accumulation of cadmium in these mice compared to those given Cd alone or CD + NTA, where cadmium was bound mainly to high molecular proteins in the liver. After 20 days, mice given CD + STPP has slightly higher body and organ retention of cadmium compared to mice given Cd alone. This may be due to a binding of cadmium to metallothione in these mice which is known to prolong the retention time of cadmium in tissue.
D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D002614:Chelating Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D009571:Nitrilotriacetic Acid / Q000494:pharmacology; D011122:Polyphosphates / Q000494:pharmacology
D002614:Chelating Agents; D011122:Polyphosphates; D002104:Cadmium; D008668:Metallothionein; D009571:Nitrilotriacetic Acid; C005692:triphosphoric acid