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L-精氨酸、二巯基丁二酸(DMSA)以及L-精氨酸与DMSA联合应用对铅中毒时组织铅动员及血压水平的影响

Effect of L-arginine, dimercaptosuccinic acid (DMSA) and the association of L-arginine and DMSA on tissue lead mobilization and blood pressure level in plumbism.

作者信息

Malvezzi C K, Moreira E G, Vassilieff I, Vassilieff V S, Cordellini S

机构信息

Departamento de Farmacologia, Instituto de Biociências, Universidade Estadual Paulista, Rubião Júnior, SP, Brasil.

出版信息

Braz J Med Biol Res. 2001 Oct;34(10):1341-6. doi: 10.1590/s0100-879x2001001000016.

Abstract

Lead (Pb)-induced hypertension is characterized by an increase in reactive oxygen species (ROS) and a decrease in nitric oxide (NO). In the present study we evaluated the effect of L-arginine (NO precursor), dimercaptosuccinic acid (DMSA, a chelating agent and ROS scavenger), and the association of L-arginine/DMSA on tissue Pb mobilization and blood pressure levels in plumbism. Tissue Pb levels and blood pressure evolution were evaluated in rats exposed to: 1) Pb (750 ppm, in drinking water, for 70 days), 2) Pb plus water for 30 more days, 3) Pb plus DMSA (50 mg kg(-1) day(-1), p.o.), L-arginine (0.6%, in drinking water), and the combination of L-arginine/DMSA for 30 more days, and 4) their respective matching controls. Pb exposure increased Pb levels in the blood, liver, femur, kidney and aorta. Pb levels in tissues decreased after cessation of Pb administration, except in the aorta. These levels did not reach those observed in nonintoxicated rats. All treatments mobilized Pb from the kidney, femur and liver. Pb mobilization from the aorta was only effective with the L-arginine/DMSA treatment. Blood Pb concentrations in Pb-treated groups were not different from those of the Pb/water group. Pb increased blood pressure starting from the 5th week. L-arginine and DMSA treatments (4th week) and the combination of L-arginine/DMSA (3rd and 4th weeks) decreased blood pressure levels of intoxicated rats. These levels did not reach those of nonintoxicated rats. Treatment with L-arginine/DMSA was more effective than the isolated treatments in mobilizing Pb from tissues and in reducing the blood pressure of intoxicated rats.

摘要

铅(Pb)诱导的高血压的特征是活性氧(ROS)增加和一氧化氮(NO)减少。在本研究中,我们评估了L-精氨酸(NO前体)、二巯基琥珀酸(DMSA,一种螯合剂和ROS清除剂)以及L-精氨酸/DMSA联合使用对铅中毒时组织铅动员和血压水平的影响。在暴露于以下情况的大鼠中评估组织铅水平和血压变化:1)铅(750 ppm,饮用水中,持续70天),2)铅加饮用水再持续30天,3)铅加DMSA(50 mg kg⁻¹ 天⁻¹,口服)、L-精氨酸(0.6%,饮用水中)以及L-精氨酸/DMSA联合使用再持续30天,4)各自相应的匹配对照组。铅暴露增加了血液、肝脏、股骨、肾脏和主动脉中的铅水平。停止给予铅后,除主动脉外,组织中的铅水平下降。这些水平未达到未中毒大鼠中观察到的水平。所有处理均使肾脏、股骨和肝脏中的铅动员。仅L-精氨酸/DMSA处理能有效使主动脉中的铅动员。铅处理组的血铅浓度与铅/水组无差异。从第5周开始铅使血压升高。L-精氨酸和DMSA处理(第4周)以及L-精氨酸/DMSA联合使用(第3周和第4周)降低了中毒大鼠的血压水平。这些水平未达到未中毒大鼠的水平。L-精氨酸/DMSA联合处理在使组织中的铅动员以及降低中毒大鼠血压方面比单独处理更有效。

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