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植入前后口服醋酸铅后的肾毒性:对痕量金属成分、金属酶和谷胱甘肽的影响

Renal toxicity after oral administration of lead acetate during pre- and post-implantation periods: effects on trace metal composition, metallo-enzymes and glutathione.

作者信息

Gupta G S, Singh J, Parkash P

机构信息

Department of Biophysics, Panjab University, Chandigarh, India.

出版信息

Pharmacol Toxicol. 1995 Mar;76(3):206-11. doi: 10.1111/j.1600-0773.1995.tb00131.x.

Abstract

The present study was undertaken to compare the effects of 10-50 mg/kg b.wt. of Pb acetate after chronic treatment through oral gavage on: (a) the distribution of trace elements such as Fe, Cu, Zn, and Mn, (b) enzyme activity of delta-amino levulinic acid dehydratase (delta-ALAD) and alkaline phosphatase, and (c) glutathione (GSH) in kidney and (d) delta-ALAD in blood of pregnant and non-pregnant mice. Treatment with Pb acetate was given on every alternate day for 4 weeks prior to mating and for 3-4 weeks until pregnancy became apparent and confirmed by laporatomy. Lead administration reduced the rate of reproduction as assessed by number of living viable embryos. During normal pregnancy renal Cu, Fe and GSH tended to decline although non-significantly and continued to do so after lead administration. Mn was considerably and significantly elevated, whereas activity of delta-ALAD (non-activated) was quite low in pregnant mice. Following administration of Pb acetate, kidneys of pregnant and non-pregnant dams accumulated Pb in a dose-dependent manner, but as compared to non-pregnant mice, Pb increase in pregnant dams was significantly lower. Pb toxicity was associated with the loss of delta-ALAD in blood and kidney, but unlike the non-activated form of delta-ALAD, the dithiothreitol-activated form of delta-ALAD declined in a significant amount. The residual activity showed a high degree of negative correlation with endogenous Pb as well as with Zn/Pb ratio. Pb toxicity did not modify renal Fe, Cu, and Zn in the pregnant state, but reduced renal Fe during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

本研究旨在比较经口灌胃慢性给予10 - 50 mg/kg体重醋酸铅后,对以下方面的影响:(a) 铁、铜、锌和锰等微量元素的分布;(b) δ-氨基-γ-酮戊酸脱水酶(δ-ALAD)和碱性磷酸酶的酶活性;(c) 肾脏中谷胱甘肽(GSH)的含量;以及(d) 怀孕和未怀孕小鼠血液中δ-ALAD的含量。在交配前每隔一天给予醋酸铅处理,持续4周,直至妊娠明显并经剖腹术确认后,再继续处理3 - 4周。通过存活胚胎数量评估,铅给药降低了繁殖率。在正常妊娠期间,肾脏中的铜、铁和GSH虽有下降趋势但不显著,铅给药后仍持续下降。锰含量显著升高,而怀孕小鼠中δ-ALAD(未激活)的活性相当低。给予醋酸铅后,怀孕和未怀孕母鼠的肾脏均以剂量依赖方式蓄积铅,但与未怀孕小鼠相比,怀孕母鼠体内铅的增加显著较低。铅毒性与血液和肾脏中δ-ALAD的损失有关,但与未激活形式的δ-ALAD不同,二硫苏糖醇激活形式的δ-ALAD显著下降。残余活性与内源性铅以及锌/铅比值呈高度负相关。铅毒性在怀孕状态下并未改变肾脏中的铁、铜和锌,但在怀孕期间降低了肾脏中的铁含量。(摘要截短至250字)

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