| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
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
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), 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
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