CHRONIC LOW-LEVEL LEAD TOXICITY IN THE RAT .3. AN INTEGRATED ASSESSMENT OF LONG-TERM TOXICITY WITH SPECIAL REFERENCE TO THE KIDNEY
CHRONIC LOW-LEVEL LEAD TOXICITY IN THE RAT .3. AN INTEGRATED ASSESSMENT OF LONG-TERM TOXICITY WITH SPECIAL REFERENCE TO THE KIDNEY
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DOI：
10.1016/0041-008x(80)90131-3
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发表时间：
1980-01-01
影响因子：
3.8
通讯作者：
GRANT, LD
中科院分区：
文献类型：
--
作者：
FOWLER, BA;KIMMEL, CA;GRANT, LD
雄性和雌性大鼠的母亲已经暴露于铅之前，在怀孕期间和哺乳期的暴露水平为0，0.5，5，25，50和250 ppm的铅作为铅-醋酸盐在饮用水中继续在各自的方案为6或9个月。6个月时，雄性和雌性动物的体重与对照组无显著差异。年龄。9个月时，250 ppm剂量组雌性动物体重显著降低。在9个月时的雄性中，在250 ppm铅时，脾脏重量显著增加，在0.5 ppm铅及以上时，肾脏重量增加。在女性的肝脏，垂体和心脏的重量受到影响，在250 ppm铅。在精子计数或精子形态、血液学特征或血清化学方面未发现显著的铅影响。血、脑、股骨和肾脏铅水平和尿ALA [氨基乙酰丙酸]排泄量与剂量显著相关。在脾脏（250 ppm）和肾脏中观察到组织学病变，表现为巨细胞/巨核（雄性从5 ppm开始;雌性从25 ppm开始）、核包涵体形成和肾近端小管细胞内Fe阳性颗粒数量增加。9个月后，这些效果更加明显。exposure.超微结构研究显示线粒体肿胀和肾脏近端小管细胞内溶酶体数量增加。能量色散X-射线微量分析，在相邻的部分进行，显示最高的细胞内铅浓度在核包涵体内肾近端小管细胞。在9个月时，发现50和250 ppm铅暴露组的肾脏线粒体呼吸抑制琥珀酸和NAD-连接底物。但不是在6个月时。线粒体δ- ALA合成酶和亚铁螯合酶，但不是δ-氨基乙酰丙酸酯酶，抑制在这些铅水平在9个月。导致可检测到的Pb效应（肾近端小管细胞中的巨细胞/巨核）的最低暴露水平为5 ppm，与11 μ g/dl的中值血液Pb浓度相关。
Male and female rats whose mothers had been exposed to Pb before and during pregnancy and lactation at exposure levels of 0, 0.5, 5, 25, 50 and 250 ppm Pb as Pb-acetate in drinking water were continued on the respective regimens for 6 or 9 mo. Body weights of males and females were not significantly different from controls at 6 mo. of age. Female body weights were significantly decreased at 250 ppm at 9 mo. In males at 9 mo., spleen weights were significantly increased at 250 ppm Pb and kidney weights were increased at 0.5 ppm Pb and above. In female livers, pituitary and heart weights were affected at 250 ppm Pb. No significant Pb effects were found in sperm counts or sperm morphology, hematology profiles or serum chemistries. Blood, brain, femur and kidney Pb levels and urinary ALA [aminolevulinic acid] excretion were significantly dose related. Histopathological lesions were noted in spleen (250 ppm) and kidney as evidenced by cytomegaly/karyomegaly (beginning at 5 ppm in males; 25 ppm in females), nuclear inclusion body formation and increased numbers of Fe-positive granules within renal proximal tubule cells. These effects were more marked after 9 mo. exposure. Ultrastructural studies revealed mitochondrial swelling and the presence of increased numbers of lysosomes within renal proximal tubule cells. Energy-dispersive X-ray microanalysis, performed on adjacent sections, showed highest intracellular Pb concentrations in nuclear inclusion bodies within renal proximal tubule cells. Inhibition of renal mitochondrial respiration for succinate and NAD-linked substrates was found in 50 and 250 ppm Pb exposure groups at 9 mo. but not at 6 mo. Mitochondrial .delta.-ALA synthetase and ferrochelatase, but not .delta.-aminolevulinic dehydratase, were inhibited at these Pb levels at 9 mo. The lowest exposure level resulting in a detectable effect of Pb (cytomegaly/karyomegaly in renal proximal tubule cells) was 5 ppm assocaited with a median blood Pb concentration of 11 .mu.g/dl.