Evidence for a synergistic interaction between cadmium and endotoxin toxicity and for nitric oxide and cadmium displacement of metals in the kidney.
Evidence for a synergistic interaction between cadmium and endotoxin toxicity and for nitric oxide and cadmium displacement of metals in the kidney.
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DOI：
10.1006/niox.2000.0295
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发表时间：
2000-08
期刊：
影响因子：
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通讯作者：
S. Satarug;J. R. Baker;Paul E.B. Reilly;Hiroyasu Esumi;Michael R. Moore
中科院分区：
文献类型：
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作者：
S. Satarug;J. R. Baker;Paul E.B. Reilly;Hiroyasu Esumi;Michael R. Moore
本研究旨在探讨镉(Cd)和脂多糖(LPS)对大鼠肝、肾锌、铜稳态的影响。选用7~8周龄雄性Wistar大鼠25只，随机分为5组：生理盐水组、生理盐水组和禁食组，单次染毒组、单纯染毒组和染毒+染毒组。分别于治疗前24 h、治疗后24 h、48 h测定血浆硝酸盐浓度、肝、肾锌、铜含量及尿中金属和硝酸盐排泄率。单独镉暴露48h，血浆硝酸盐水平增加近2倍，尿硝酸盐排泄无变化，而内毒素处理使血浆硝酸盐水平增加10倍，尿硝酸盐排泄增加4倍。与染毒前相比，染毒24小时后给予内毒素可使大鼠血浆硝酸盐浓度增加10倍，尿硝酸盐排泄增加100倍。这些结果表明，镉和脂多糖毒性之间存在协同作用。染镉组大鼠肝组织锌含量明显升高，而内毒素对肝组织锌、铜含量无明显影响。与之形成鲜明对比的是，染镉或脂多糖的动物肾脏中锌和铜的含量分别下降了16%和36%。对测量变量的相关分析表明，肾脏铜含量与血浆硝酸盐浓度呈负相关，而第3天尿铜排泄量与当日尿硝酸盐和镉排泄量均呈显著正相关。线性回归分析表明，尿铜排泄量的变化有20%与同一天的尿镉排泄量有关。结论：镉或脂多糖引起的肾组织铜含量降低可能是由于镉和金属硫蛋白结合的铜没有置换所致。
This study was undertaken to examine changes in Zn and Cu homeostasis in the liver and kidney of rats caused by cadmium (Cd) or lipopolysaccharide (LPS) administration. Twenty-five male, 7- to 8-week-old Wistar rats were divided into five groups: saline only treatment, saline treatment and food deprivation, exposure to a single dose of Cd, exposure to LPS alone, and exposure to Cd + LPS. Changes in plasma nitrate concentrations and hepatic and renal 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 2-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. Administration 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 compared to the rates prior to LPS administration. These results indicate a synergistic interaction between Cd and LPS toxicity. Cd exposure also caused a marked increase in hepatic Zn levels, but LPS did not cause any changes in hepatic Zn or Cu content. In sharp contrast, both Zn and Cu contents were decreased in the kidneys by 16 and 36% in animals exposed to Cd or LPS. A correlation analysis of measured variables reveals that renal Cu contents were inversely associated with plasma nitrate concentrations while urinary Cu excretion on day 3 showed a strong positive correlation with both urinary nitrate and Cd excretions on the same day. A linear regression analysis shows 20% of the variation in urinary Cu excretion was associated with urinary Cd excretion on the same day. It is concluded that reductions in renal Cu contents caused by Cd or LPS administration may be a result of Cd and NO displacement of Cu previously bound to metallothionein.