An explanation for strain and sex differences in renal uptake of methylmercury in mice.
The present investigation was designed to elucidate the mechanism for strain and sex differences in renal methylmercury accumulation, in five mouse strains, viz. BALB/cA, C57BL/6N, CBA/JN, C3H/HeN and ICR. Strain and sex comparisons of factors which influence renal mercury accumulation were made. Strain and sex differences were observed in renal mercury accumulation 4 h after methylmercuric chloride (MMC) (1 mumol/kg, s.c.) injection. Glutathione (GSH) content in liver and kidney showed significant strain and sex differences. Pretreatment with 1,2-dichloro-4-nitrobenzene (DCNB), to deplete hepatic GSH without affecting renal non-protein thiol (NPSH) level, led to a dose-dependent decrease in hepatic and plasma GSH concentrations that correlated with decreased mercury levels in the kidney 10 min after MMC (1 mumol/kg, i.v.) injection. This indicates that hepatic and plasma GSH levels are related to mercury accumulation into the kidney. Renal gamma-glutamyltranspeptidase (gamma-GTP) activity significantly varied among the strains, and in BALB/cA and ICR, renal gamma-GTP activity in males was about 2-fold higher than that in females. Renal gamma-GTP activity was also correlated with the renal mercury content. These results suggest that strain and sex differences in renal accumulation of mercury are attributable to differences in tissue GSH content and possibly to differences in renal gamma-GTP activity.
Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
T
T
Tanaka
A
A
Naganuma
K
K
Kobayashi
N
N
Imura
D000818:Animals; D005260:Female; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008767:Methylmercury Compounds / Q000493:pharmacokinetics*; D051379:Mice; D008815:Mice, Inbred Strains; D012727:Sex Characteristics; D013045:Species Specificity; D014018:Tissue Distribution; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D008767:Methylmercury Compounds; D005723:gamma-Glutamyltransferase; D005978:Glutathione; C004925:methylmercuric chloride