Strain difference in sensitivity of mice to renal toxicity of inorganic mercury.
Inorganic mercury has a high affinity for the kidneys and causes acute renal failure. The present investigation was designed to determine the cause of the strain difference in sensitivity of mice to the renal toxicity of inorganic mercury. Renal damage caused by HgCl2 was estimated by histopathological and biochemical assessment, such as increase in blood urea nitrogen and plasma creatinine levels, and was found to be more remarkable in C3H/He than in C57BL/6 mice. Increase in renal lipid peroxidation in C3H/He was greater than that in C57BL/6 mice. However, no strain difference was observed in renal activities of glutathione (GSH) peroxidase, superoxide dismutase and GSH S-transferase in HgCl2-untreated mice. The GSH content and activities of catalase and GSSG reductase in kidney of HgCl2-untreated mice were higher in C3H/He than in C57BL/6. Background level of renal metallothionein content and the extent of metallothionein induction by HgCl2 showed no strain difference. On the other hand, renal mercury accumulation was higher and urinary mercury excretion was lower in C3H/He than in C57BL/6. The activity of renal gamma-glutamyltranspeptidase (gamma-GTP), which plays a key role in renal mercury accumulation, was higher in C3H/He than in C57BL/6. Furthermore, the increase in blood urea nitrogen by HgCl2, renal mercury accumulation and renal gamma-GTP activity in B6C3F1 mice were intermediate between those of the parent strains. These results suggest that the strain difference in renal toxicity of inorganic mercury seems to be caused by the discrepancy in renal mercury accumulation, and therefore, renal gamma-GTP may be an important factor determining the susceptibility of mice to the toxic action of inorganic mercury.
Tanaka-Kagawa
T
T
Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108, Japan.
Suzuki
M
M
Naganuma
A
A
Yamanaka
N
N
Imura
N
N
D000818:Animals; D005260:Female; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008628:Mercury / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine; D008668:Metallothionein / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013045:Species Specificity
D008668:Metallothionein; D008628:Mercury; D005978:Glutathione