Sohn O S, Blackwell L, Mathis J, Asaad W W, Reddy B S, el-Bayoumy K
Division of Biochemical Pharmacology, American Health Foundation, Valhalla, NY 10595.
Drug Metab Dispos. 1991 Sep-Oct;19(5):865-70.
Benzylselenocyanate (BSC), a synthetic organoselenium compound less toxic than sodium selenite (Na2SeO3), has been demonstrated to inhibit the development of neoplasia in several experimental animal models. We examined the excretion and tissue distribution of total Se after acute administration of BSC compared to Na2SeO3. Male F344 rats were treated po with approximately one-tenth of the LD50 values, our estimate of highest non-toxic dose. The doses administered were 9.85 mg/kg in the case of BSC and 4.35 mg/kg in the case of Na2SeO3. The rats were sacrificed at 1, 6, 24, 72, or 120 hr to obtain biological samples. The levels of total Se were determined by graphite furnace atomic absorption spectrophotometry following microwave digestion. In serum, the highest Se level was observed at 6 hr after administration of either BSC or Na2SeO3: 1.34 +/- 0.07 (mean +/- SE), or 2.09 +/- 0.11 micrograms/ml of serum, respectively. In urine and feces, the cumulative percentages of doses excreted within 3 days of BSC or Na2SeO3 treatment were, respectively, as follows: 11.36 +/- 0.82% and 18.33 +/- 0.77% in urine; and 6.67 +/- 0.66% and 31.14 +/- 4.66% in feces. Among the tissues of BSC-treated rats, the kidneys were found to have the highest Se levels throughout the experimental period (as much as 29 micrograms/g of tissue at 72 hr), followed by liver, small intestine, large intestine, lung, pancreas, heart, and spleen. The results indicate that Se from BSC-treated animals is excreted very slowly and is retained in the organs for a much longer period compared to rats treated with Na2SeO3. Whether the slow excretion and prolonged retention of BSC and/or its metabolites play a role in its chemopreventive action is currently under investigation.
苄基硒氰酸盐(BSC)是一种合成有机硒化合物,其毒性低于亚硒酸钠(Na2SeO3)。在几种实验动物模型中,已证明它能抑制肿瘤形成。我们研究了急性给予BSC后与Na2SeO3相比,总硒的排泄和组织分布情况。雄性F344大鼠经口给予约为半数致死量(LD50)十分之一的剂量,这是我们估计的最高无毒剂量。给予的剂量分别为:BSC组9.85 mg/kg,Na2SeO3组4.35 mg/kg。在1、6、24、72或120小时处死大鼠以获取生物样本。微波消解后,采用石墨炉原子吸收分光光度法测定总硒水平。在血清中,给予BSC或Na2SeO3后6小时观察到最高硒水平,分别为1.34±0.07(均值±标准误)或2.09±0.11微克/毫升血清。在尿液和粪便中,BSC或Na2SeO3处理后3天内排泄剂量的累积百分比分别如下:尿液中为11.36±0.82%和18.33±0.77%;粪便中为6.67±0.66%和31.14±4.66%。在接受BSC处理的大鼠组织中,整个实验期间肾脏中的硒水平最高(72小时时高达29微克/克组织),其次是肝脏、小肠、大肠、肺、胰腺、心脏和脾脏。结果表明,与接受Na2SeO3处理的大鼠相比,接受BSC处理的动物体内的硒排泄非常缓慢,且在器官中保留的时间长得多。目前正在研究BSC及其代谢产物的缓慢排泄和长时间保留是否在其化学预防作用中发挥作用。