Wahba Z Z, Coogan T P, Rhodes S W, Waalkes M P
Inorganic Carcinogenesis Section, National Cancer Institute-FCRDC, MD 21702.
J Toxicol Environ Health. 1993 Feb;38(2):171-82. doi: 10.1080/15287399309531710.
Selenium prevents the toxicity of the carcinogenic metal cadmium through undefined mechanisms. In this study, we determined the effects of selenium on cadmium toxicokinetics and on the ability of cadmium to induce metallothionein, a metal-binding protein that is thought to confer tolerance to cadmium toxicity. To assess the acute protective effects of selenium, male Wistar (WF/NCr) rats were given selenium (as SeO2; 10 mumol/kg, sc) at -24, 0, and +24 h relative to cadmium (as CdCl2; 45 mumol/kg, sc). Over a 14-d period this dose of cadmium killed 6 out of 10 rats, while 100% of the cadmium-treated rats given concurrent selenium treatments survived. The acute increases in testicular weight that were seen with cadmium, indicative of edematous damage, were also prevented by concurrent selenium treatments. Further studies assessed the distribution and excretion of cadmium and its ability to induce metallothionein in rats given 40 mumol Cd/kg, sc, at time 0 and selenium (10 mumol/kg, sc) at -24 and 0 h. Selenium treatments enhanced cadmium accumulation at 24 h in the liver (23%), testes (145%), and epididymis (35%) but reduced renal accumulation by more than half. Urine samples, collected at 0-3, 3-6, and 6-24 h following cadmium administration, indicated a markedly reduced excretion of cadmium in selenium treated rats during all time periods. The synthesis of metallothionein was stimulated to a much lesser extent by cadmium in selenium-treated rat kidney (41% decrease) but was unaffected in liver. The levels of cadmium-binding proteins within the testes were markedly reduced by cadmium treatment, an effect unmodified by selenium treatments. These results suggest selenium prevents acute cadmium toxicity through a mechanism that does not involve induction of metallothionein and in spite of a markedly enhanced retention of cadmium.
硒通过不明机制预防致癌金属镉的毒性。在本研究中，我们确定了硒对镉毒代动力学以及镉诱导金属硫蛋白能力的影响，金属硫蛋白是一种金属结合蛋白，被认为可赋予对镉毒性的耐受性。为评估硒的急性保护作用，在相对于镉（以CdCl₂；45 μmol/kg，皮下注射）的-24、0和+24小时，给雄性Wistar（WF/NCr）大鼠注射硒（以SeO₂；10 μmol/kg，皮下注射）。在14天的时间里，该剂量的镉使10只大鼠中的6只死亡，而同时接受硒处理的镉处理大鼠100%存活。镉导致的睾丸重量急性增加表明存在水肿性损伤，同时进行的硒处理也可预防这种情况。进一步的研究评估了在0时给予40 μmol Cd/kg皮下注射以及在-24和0小时给予硒（10 μmol/kg，皮下注射）的大鼠中镉的分布和排泄情况，以及其诱导金属硫蛋白的能力。硒处理在24小时时增强了镉在肝脏（23%）、睾丸（145%）和附睾（35%）中的蓄积，但使肾脏中的蓄积减少了一半以上。在镉给药后的0 - 3、3 - 6和6 - 24小时收集的尿液样本表明，在所有时间段内，硒处理大鼠的镉排泄量均显著降低。在硒处理的大鼠肾脏中，镉对金属硫蛋白合成的刺激程度要小得多（降低41%），但在肝脏中不受影响。镉处理使睾丸内镉结合蛋白水平显著降低，硒处理对此效应无改变。这些结果表明，硒通过一种不涉及诱导金属硫蛋白的机制预防急性镉毒性，尽管镉的潴留明显增强。
