Effect of low-level cadmium intake to maternal bone metabolism.

低水平镉摄入对母体骨代谢的影响。

• 批准号: 16590481
• 负责人: OHTA Hisayoshi
• 金额: $ 0.83万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590481/
• 关键词: Cadmium; Maternal bone metabolism; Bone mineral density; Load of lactation; Osteoid volume; Bone bending strength; Renal dysfunction; maternal-tofetus transport

Effects of cadmium(Cd) intake together with delivery-lactation to maternal renal function and bone metabolism were investigated. Female Wistar rats (6 weeks old) were given Cd (as CdCl2) at a dose of 1, 2, and 5 mgCd/kg/day by gastric tube daily for 6 consecutive days a week for 10 weeks. After delivering, mother rats lactated to newborn rats of 4 male and female each. Cd was given continuously during three times of pregnancy and lactation to mother rats. Urinary excretion of enzymes (β2-MG, NAG, GST), amino acids, protein, and calcium were determined to evaluate renal function. The urinary excretion of pyridinoline (Pyr) and deoxypyridinoline (DPyr) and plasma intact-osteocalcin (BGP) was also determined to evaluate bone metabolism. Bone mineral density and bone bending strength of the femur of mother rats were also determined respectively by the microdensitometry (MD) method and by the 3-point bending analysis.Prominent tendency of renal dysfunction of lowest Cd group (1mgCd/kg group … More ), a similar level with a human daily Cd intake, was not observed in mother rats by Cd intake and lactation, as shown by increased urinary excretion of β2-MG, NAG, and protein. The dose-dependent decrease of bone mineral density (BMD), bone maximum bending strength (BMBS), bone mineral content(BMC), and cortical thickness index (CTI) was found in mother rats after the third pregnancy and lactation together with increased Cd exposure, especially in the groups of 2mgCd/kg and 5mgCd/kg. The increase of relative osteoid volume in the femur tissue was found in all group, depending on the increased frequency of pregnancy and lactation. This increased relative osteoid volume was more prominent in all experimental groups of 1mgCd/kg, 2mgCd/kg and 5mgCd/kg, depending on the increased Cd exposure and on the frequency of pregnancy and lactation. However, the prominent meaningful tendency in the biochemical indexes reflecting renal dysfunction and bone metabolism disorder was not observed without the excretion of B2-MG, DPyr, and Ca in the 5mgCd/kg group. Namely, the prominent increased urinary excretion of Dpyr, B2-MG and Ca was found corresponding to an increased frequency of pregnancy and lactation in the 5mgCd/kg group. The significant increase of metallothionein(MT) was not found in uterus tissue for Cd transfer of materal-to-fetrus. But the participation of MT for the inhibition of Cd transfer into fetus was suggested. From the distribution in kidney and liver of Cd on newborn infant of first day old after delivery, it was suggested that Cd of the chemical form of non-Cd-MT leaked into fetus through blood-placenta barrier ad accumulated in liver.In conclusion, it was suggested that low-level Cd intake modulate together with pregnancy and lactation the bone metabolism of mother rat, especially the promotion of bone absorption. It was thought that the lactation is an important affecting factor in the evaluation of Cd effect to bone mineralization. Akso, it was suggested that the decreased BMD of maternal femur was recovered in case of both stop and continuation of Cd intake after nursing. Less

本文研究了镉摄入与分娩-哺乳期对母体肾功能和骨代谢的影响。雌性Wistar大鼠（6周龄）给予镉（CdCl 2）的剂量为1，2，和5 mgCd/kg/天，每天通过胃管，每周连续6天，共10周。母鼠分娩后，产下仔鼠，雌雄各4只。在母鼠妊娠期和哺乳期连续三次给予镉。测定尿酶（β2-MG、NAG、GST）、氨基酸、蛋白质和钙的排泄，以评估肾功能。测定尿吡啶啉（Pyr）、脱氧吡啶啉（DPyr）排泄量和血浆骨钙素（BGP）水平，评价骨代谢。采用显微密度法（MD）和三点弯曲法分别测定母鼠股骨骨密度和骨弯曲强度，低镉组（1 mgCd/kg组）肾功能损害趋势明显 ...更多信息 而在哺乳期和镉摄入组，β2-MG、NAG和蛋白质的尿排泄量均明显增加。随着染镉量的增加，孕3次及哺乳期母鼠的骨密度（BMD）、骨最大弯曲强度（BMBS）、骨矿含量（BMC）和皮质厚度指数（CTI）均呈剂量依赖性下降，以2 mgCd/kg和5 mgCd/kg组最为明显。各组大鼠股骨组织中相对类骨质体积均增加，这取决于妊娠和哺乳频率的增加。这种增加的相对类骨质体积在1 mgCd/kg、2 mgCd/kg和5 mgCd/kg的所有实验组中更为突出，这取决于镉暴露的增加以及怀孕和哺乳的频率。而在5 mgCd/kg组，除B2-MG、DPyr和Ca外，反映肾功能不全和骨代谢紊乱的生化指标无显著有意义的趋势。5 mgCd/kg组大鼠尿Dpyr、B2-MG和Ca排泄量显著增加，妊娠和哺乳次数增加。子宫组织中金属硫蛋白（MT）的含量在镉的母胎转运过程中未见明显增加。但MT可能参与了镉向胎儿转运的抑制作用。从出生后第1天的新生儿肾脏和肝脏中Cd的分布情况来看，Cd以非Cd-MT的化学形态通过血-胎盘屏障渗漏到胎鼠体内，并在肝脏中蓄积，提示低水平Cd摄入与妊娠和哺乳共同调节母鼠的骨代谢，尤其是促进骨吸收。认为哺乳期是评价镉对骨矿化作用的重要影响因素。提示经护理后，无论停服或继续服镉，降低的股骨骨密度均可恢复。少

项目成果

Tolerable daily intake of cadmium in human estimated based on oral cadmium administration in female rats.

根据雌性大鼠口服镉估算人类每日可耐受镉摄入量。

• 发表时间: 2004
• 期刊: Biomed Res Trace Elements 15(4)
• 作者: Yohei Ohkawa;Hisayoshi Ohta;Yasuhiro Nakamura
• 通讯作者: Yasuhiro Nakamura

Low-level cadmium intake together with lactation modulate bone mrtabolism and renal function in mother rats.

低水平的镉摄入与哺乳一起调节母鼠的骨代谢和肾功能。

• 发表时间: 2004
• 期刊: The Journal of Trace Elements in Experimental Medicine 17(4)
• 作者: Mori K;Yoshida K;Tani JI;Hoshikawa S;Ito S;Watanabe C.;Hisayosi Ohta
• 通讯作者: Hisayosi Ohta

カドミウムの骨影響・イタイイタイ病の骨病変に関する研究-低濃度カドミウム曝露の骨代謝に及ぼす影響評価に関する研究-

镉对痛痛病骨骼及骨病变影响的研究 - 评估低浓度镉暴露对骨代谢影响的研究 -

• 发表时间: 2005
• 期刊: 環境保健レポート 69
• 作者: Hisayoshi Ohta;Yasuhiro Nakasmura;Yohei Ohkawa;Kenichi Ohba;Yoshifumi Ohmori;Matsui T. et al.;堤 明純;太田 久吉
• 通讯作者: 太田 久吉

Low-level cadmium intake together with lactation modulates bone mineralization of femur in mother rats

低水平镉摄入与哺乳一起调节母鼠股骨骨矿化

• 发表时间: 2005
• 期刊: Kankyou Hoken Report 69
• 作者: Hisayoshi Ohta;Maejima Yukia;Taeko Nakagawa;Yashuhiro Nakamura;Hiroki Fujita;Hiroyuki Aikawa
• 通讯作者: Hiroyuki Aikawa

Adverse effect of low-level cadmium intake and the role of metallo-thionein on cadmium transport from mother rats to newborn rats.

低水平镉摄入的不利影响以及金属硫蛋白对镉从母鼠转运至新生鼠的作用。

• 发表时间: 2004
• 期刊: The Journal of Trace Elements in Experimental Medicine 17(4)
• 作者: Yoshida;M.;Watanabe;C.;Kishimoto M.;Yasutake;A.;Satoh;M.;Sawada;M.;Akama;Y.;Tsutsumi A;Yasuhiro Nakamura
• 通讯作者: Yasuhiro Nakamura