Brzóska Malgorzata M, Rogalska Joanna, Galażyn-Sidorczuk Malgorzata, Jurczuk Maria, Roszczenko Alicja, Kulikowska-Karpińska Elżbieta, Moniuszko-Jakoniuk Janina
Department of Toxicology, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland.
Department of Toxicology, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland.
Toxicology. 2007 Jul 31;237(1-3):89-103. doi: 10.1016/j.tox.2007.05.001. Epub 2007 May 5.
The aim of the present study is to investigate, based on the rat model of moderate and relatively high human exposure to cadmium (Cd), whether zinc (Zn) supplementation may prevent Cd-induced disorders in bone metabolism. For this purpose, male Wistar rats received Cd (5 and 50mg/l) or/and Zn (30 and 60mg/l) in drinking water for 6 and 12 months. Bone densitometry and biochemical markers of bone turnover were used to assess the effects of Cd or/and Zn. Bone mineral content (BMC) and density (BMD) were measured in the femur. Serum osteocalcin (OC) and alkaline phosphatase in trabecular (bT-ALP) and cortical (bC-ALP) bone were determined as bone formation markers, and carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in serum were measured as bone resorption marker. Serum concentration of calcium (Ca) and its renal handling, as well as Zn and Cd concentrations in the serum/blood, urine and femur were evaluated as well. The exposure to 5 and 50mg Cd/l (0.340+/-0.026 and 2.498+/-0.093mg Cd/kg body wt/24h, respectively), in a dose and duration dependent manner, affected bone turnover (inhibited bone formation and stimulated its resorption) and disturbed bone mineralization (decreased BMC, BMD and Zn concentration). Zn supply at the concentration of 30 and 60mg/l (1.904+/-0.123 and 3.699+/-0.213mg/kg body wt/24h, respectively) during Cd exposure influenced the Cd-induced disorders in bone metabolism. Zn administration to the Cd-exposed rats enhanced the bone ALP activity and prevented Cd-induced bone resorption, but had no statistically significant effect on BMC and BMD; however, mean values of the densitometric parameters in the rats receiving both Cd and Zn were higher than in those treated with Cd alone. Moreover, Zn supplementation at both levels of Cd exposure was found to prevent Cd accumulation in the femur and the Cd-induced decrease in bone Zn concentration. The results of the present study allow the conclusion that Zn supplementation during Cd exposure may partly protect from disorders in bone metabolism. The influence of Zn may be accompanied by its ability to prevent Cd-induced Zn deficiency and to decrease Cd accumulation in bone tissue. The findings seem to indicate that enhanced dietary intake of Zn in subjects chronically exposed to moderate and relatively high Cd levels may have a protective influence on the skeleton.
本研究的目的是基于人类中度和相对高度镉(Cd)暴露的大鼠模型,探究补充锌(Zn)是否可以预防Cd诱导的骨代谢紊乱。为此,雄性Wistar大鼠在6个月和12个月的时间里饮用含Cd(5和50mg/l)或/和Zn(30和60mg/l)的水。采用骨密度测定法和骨转换生化标志物来评估Cd或/和Zn的作用。测量股骨的骨矿物质含量(BMC)和骨密度(BMD)。测定血清骨钙素(OC)以及小梁骨(bT-ALP)和皮质骨(bC-ALP)中的碱性磷酸酶作为骨形成标志物,并测量血清中I型胶原羧基末端交联肽(CTX)作为骨吸收标志物。还评估了血清钙(Ca)浓度及其肾脏处理情况,以及血清/血液、尿液和股骨中的Zn和Cd浓度。以剂量和时间依赖的方式暴露于5和50mg Cd/l(分别为0.340±0.026和2.498±0.093mg Cd/kg体重/24小时)会影响骨转换(抑制骨形成并刺激其吸收)并扰乱骨矿化(降低BMC、BMD和Zn浓度)。在Cd暴露期间以30和60mg/l(分别为1.904±0.123和3.699±0.213mg/kg体重/24小时)的浓度供应Zn会影响Cd诱导的骨代谢紊乱。对Cd暴露大鼠施用Zn可增强骨ALP活性并预防Cd诱导的骨吸收,但对BMC和BMD没有统计学上的显著影响;然而,同时接受Cd和Zn的大鼠中骨密度参数的平均值高于仅接受Cd处理的大鼠。此外,发现在两种Cd暴露水平下补充Zn均可预防Cd在股骨中的蓄积以及Cd诱导的骨Zn浓度降低。本研究结果得出结论,在Cd暴露期间补充Zn可能部分预防骨代谢紊乱。Zn的影响可能与其预防Cd诱导的Zn缺乏以及降低骨组织中Cd蓄积的能力有关。研究结果似乎表明,在长期暴露于中度和相对高度Cd水平的受试者中增加饮食中Zn的摄入量可能对骨骼有保护作用。