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

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
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DOI:
10.1590/s0100-879x2001001000016
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发表时间:
2001-10-01
影响因子:
2.3
通讯作者:
Cordellini, S
Cordellini, S
中科院分区:
医学4区
文献类型:
--
作者:
Malvezzi, CK;Moreira, EG;Cordellini, S

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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,螯合剂和ROS清除剂)的影响,以及L-精氨酸/DMSA对铅中毒组织铅动员和血压水平的影响。在暴露于以下物质的大鼠中评价组织铅水平和血压变化:1)铅(750 ppm,在饮用水中,持续70天),2)铅加水再持续30天,3)铅加DMSA(50 mg kg(-1)d(-1),po)、L-精氨酸(0.6%,饮水)和L-精氨酸/DMSA联合给药30 d; 4)其各自的配对对照。铅暴露增加铅水平的血液,肝脏,股骨,肾脏和主动脉。停止铅给药后,除主动脉外,各组织中的pH值均下降。这些水平没有达到在未中毒大鼠中观察到的水平。所有治疗动员铅从肾脏,股骨和肝脏。铅动员从主动脉是唯一有效的L-精氨酸/DMSA治疗。铅处理组的血铅浓度与铅/水组的血铅浓度没有差异。铅从第5周开始使血压升高。L-精氨酸和DMSA处理(第4周)和L-精氨酸/DMSA Ord和第4周)的组合降低了中毒大鼠的血压水平。这些水平没有达到非中毒大鼠的水平。用L-精氨酸/DMSA处理比单独处理更有效地动员铅从组织和降低中毒大鼠的血压。
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), po), 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. Ph 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 Ord 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.