Liu Y, Liu J, Klaassen C D
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160-7417, USA.
Toxicol Appl Pharmacol. 2001 Sep 15;175(3):253-9. doi: 10.1006/taap.2001.9244.
Cadmium (Cd) is an environmental pollutant and is toxic to many tissues. Food is the primary source of Cd exposure for the general population. Metallothionein (MT), a cysteine-rich, Cd-binding protein, plays an important role in Cd detoxication. However, the role of MT in Cd absorption and distribution is still controversial. For example, some reports assert that MT in the intestine decreases Cd absorption and increases its distribution to the kidney, relative to the liver. Therefore, to further clarify the role of MT in Cd absorption and tissue distribution, MT-I/II knockout (MT-null) mice and their parental background wild-type mice were given a single dose of (109)Cd (1-300 micromol/kg po or 0.1-30 micromol/kg iv). Cd content in 15 organs was determined 4 h after Cd administration by gamma scintillation spectrometry. Approximately 60% of the Cd administered iv was retained in liver, and about 5% was retained in kidney in both MT-null and wild-type mice. The distribution of iv administered Cd was independent of dose. In contrast, when administered po, approximately 0.15% of the lowest dose (1 micromol/kg) and 0.75% of the highest dose (300 micromol/kg) was detected in the liver of both MT-null and wild-type mice. Similarly in kidney, approximately 0.05% of the dose was detected after the lowest dose and about 0.15% after the higher doses in both MT-null and wild-type mice. In summary, this study demonstrates that the absorption and initial distribution of orally administered Cd is dose dependent but is not influenced by MT.
镉(Cd)是一种环境污染物,对许多组织都有毒性。食物是普通人群镉暴露的主要来源。金属硫蛋白(MT)是一种富含半胱氨酸的镉结合蛋白,在镉解毒过程中起重要作用。然而,MT在镉吸收和分布中的作用仍存在争议。例如,一些报告称,相对于肝脏,肠道中的MT会减少镉的吸收,并增加其向肾脏的分布。因此,为了进一步阐明MT在镉吸收和组织分布中的作用,给MT-I/II基因敲除(MT缺失)小鼠及其亲本背景野生型小鼠单次给予(109)Cd(口服1 - 300微摩尔/千克或静脉注射0.1 - 30微摩尔/千克)。在给予镉后4小时,通过γ闪烁光谱法测定15个器官中的镉含量。静脉注射的镉在MT缺失小鼠和野生型小鼠中,约60%保留在肝脏中,约5%保留在肾脏中。静脉注射镉的分布与剂量无关。相比之下,口服给药时,在MT缺失小鼠和野生型小鼠的肝脏中均检测到,最低剂量(1微摩尔/千克)的约0.15%和最高剂量(300微摩尔/千克)的约0.75%。同样在肾脏中,MT缺失小鼠和野生型小鼠在最低剂量后检测到约0.05%的剂量,较高剂量后约为0.15%。总之,本研究表明,口服镉的吸收和初始分布是剂量依赖性的,但不受MT的影响。