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Cd-metallothionein nephrotoxicity in inbred strains of mice
L E Sendelbach1, W C Kershaw, F Cuppage
1Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.
Abstract:
Genetic differences in the acute hepatic and testicular toxicity of Cd occur among different strains of mice. However, it is not known whether genetic variation to the renal damage caused by Cd-metallothionein (CdMT) exists. Therefore, male mice of the C3H/HeJ, C57/Bl10, CBA/CA, and DBA/2J strains, previously shown to differ in hepatic and testicular injury due to Cd, were treated with CdMT at dosages of 0.2, 0.4, 0.8, and 1.6 mg/kg (sc). For all strains of mice, tissue accumulation of Cd occurred predominantly in kidney, which had two to three times as much Cd as liver, while testes had no measurable amounts of Cd. Hepatic and renal metallothionein (MT) concentrations were increased with increasing dosage of CdMT, and no differences between strains were demonstrated. Urinary glucose was increased significantly at the three highest dosages of CdMT, with no differences between strains. At each dose level, light microscopic manifestations of CdMT nephropathy did not differ between strains. In summary, all CdMT-treated strains of mice responded similarly with respect to all measured renal parameters (accumulation of Cd and MT and nephrotoxicity). Unlike the strain differences in hepatic and testicular injury from Cd in these strains of mice, CdMT nephrotoxicity shows no such genetic variation.
Insights
Genetic variation does not affect cadmium-metallothionein (CdMT) induced kidney damage in mice. All tested mouse strains showed similar renal responses to CdMT, unlike their varied responses to cadmium alone.
Area of Science:
- Toxicology
- Genetics
- Nephrology
Background:
- Genetic differences influence cadmium (Cd) toxicity in mouse liver and testes.
- The impact of genetic variation on cadmium-metallothionein (CdMT) induced kidney damage is unknown.
Purpose of the Study:
- To investigate whether genetic variation exists in the renal toxicity of CdMT.
Main Methods:
- Male mice from four strains (C3H/HeJ, C57/Bl10, CBA/CA, DBA/2J) were treated with varying dosages of CdMT.
- Kidney and liver Cd accumulation, metallothionein (MT) concentrations, urinary glucose levels, and light microscopic renal damage were assessed.
Main Results:
- Cd predominantly accumulated in the kidneys of all mouse strains.
- Increased CdMT dosage led to higher kidney MT concentrations and elevated urinary glucose, with no strain-specific differences.
- No significant differences in CdMT-induced nephropathy were observed among the mouse strains.
Conclusions:
- CdMT nephrotoxicity does not exhibit genetic variation in the studied mouse strains.
- Unlike hepatic and testicular Cd toxicity, renal damage from CdMT is consistent across different genetic backgrounds in mice.