S. Satarug et al., Evidence for a synergistic interaction between cadmium and endotoxin toxicity and for nitric oxide and cadmium displacement of metals in the kidney, NITRIC OXID, 4(4), 2000, pp. 431-440
This study was undertaken to examine changes in Zn and Cu homeostasis in th
e liver and kidney of rats caused by cadmium (Cd) or lipopolysaccharide (LP
S) administration. Twenty-five male, 7- to 8-week-old Wistar rats were divi
ded into five groups: saline only treatment, saline treatment and food depr
ivation, exposure to a single dose of Cd, exposure to LPS alone, and exposu
re to Cd + LPS. Changes in plasma nitrate concentrations and hepatic and re
nal Zn and Cu contents were measured together with urinary excretion rates
for the metals and nitrate on 3 consecutive days: 24 h before treatment and
24 and 48 h after treatments. Cd exposure alone for 48 h caused a nearly a
-fold increase in plasma nitrate levels with no changes in urinary nitrate
excretion whereas LPS treatment caused plasma nitrate levels to increase by
10-fold and urinary nitrate excretion to increase by 4-fold. Administratio
n of LPS 24 h after Cd exposure caused a 10-fold increase in plasma nitrate
concentrations and a 100-fold increase in urinary nitrate excretion compar
ed to the rates prior to LPS administration. These results indicate a syner
gistic interaction between Cd and LPS toxicity. Cd exposure also caused a m
arked increase in hepatic Zn levels, but LPS did not cause any changes in h
epatic Zn or Cu content. In sharp contrast, both Zn and Cu contents were de
creased in the kidneys by 16 and 36% in animals exposed to Cd or LPS. A cor
relation analysis of measured variables reveals that renal Cu contents were
inversely associated with plasma nitrate concentrations while urinary Cu e
xcretion on day 3 showed a strong positive correlation with both urinary ni
trate and Cd excretions on the same day. A linear regression analysis shows
20% of the variation in urinary Cu excretion was associated with urinary C
d excretion on the same day. It is concluded that reductions in renal Cu co
ntents caused by Cd or LPS administration may be a result of Cd and NO disp
lacement of Cu previously bound to metallothionein. (C) 2000 Academic Press
.