Barbosa Fernando, Sertorio Jonas T C, Gerlach Raquel F, Tanus-Santos Jose E
Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences of Ribeirao Preto, Av. do Cafe, s/n, 14040-903 Ribeirao Preto, SP, Brazil.
Arch Toxicol. 2006 Dec;80(12):811-6. doi: 10.1007/s00204-006-0111-3.
Lead exposure has been associated with increased cardiovascular risk, which may result, at least in part, from lead-induced increases in oxidative stress and depressed nitric oxide (NO) availability. However, no previous clinical study has examined whether lead exposure is associated with significant effects on biomarkers of NO activity (plasma nitrites, nitrates, and cyclic guanosine 3',5'-monophosphate; cGMP). We investigated whether there is an association between the circulating concentrations of nitrites, nitrates, and cGMP and the concentrations of lead in whole blood (B-Pb) or plasma (P-Pb) from 62 lead-exposed subjects (30 men and 32 women). P-Pb was determined by inductively coupled plasma mass spectrometry and B-Pb by graphite furnace atomic absorption spectrometry. Plasma nitrite and nitrate concentrations were measured using an ozone-based chemiluminescence assay. Plasma cGMP concentrations were measured using a commercial enzyme immunoassay. We found a negative correlation between plasma nitrite and B-Pb concentrations (r = -0.358; P = 0.004), and between plasma nitrite and P-Pb concentrations (r = -0.264; P = 0.038), thus suggesting increased inhibition of NO formation with increasing B-Pb or P-Pb concentrations. However, no significant correlations were found between plasma nitrate or cGMP and B-Pb or P-Pb concentrations (all P > 0.05). These findings suggest a significant inhibitory effect of lead exposure on NO formation and provide clinical evidence for a biological mechanism possibly involved the association between lead exposure and increased cardiovascular risk.
铅暴露与心血管风险增加有关，这可能至少部分是由于铅导致氧化应激增加和一氧化氮（NO）可用性降低所致。然而，以前没有临床研究检查过铅暴露是否与对NO活性生物标志物（血浆亚硝酸盐、硝酸盐和环磷酸鸟苷；cGMP）有显著影响。我们调查了62名铅暴露受试者（30名男性和32名女性）的亚硝酸盐、硝酸盐和cGMP循环浓度与全血（B-Pb）或血浆（P-Pb）中铅浓度之间是否存在关联。P-Pb通过电感耦合等离子体质谱法测定，B-Pb通过石墨炉原子吸收光谱法测定。血浆亚硝酸盐和硝酸盐浓度使用基于臭氧的化学发光分析法测量。血浆cGMP浓度使用商业酶免疫分析法测量。我们发现血浆亚硝酸盐与B-Pb浓度之间呈负相关（r = -0.358；P = 0.004），以及血浆亚硝酸盐与P-Pb浓度之间呈负相关（r = -0.264；P = 0.038），因此表明随着B-Pb或P-Pb浓度增加，NO生成的抑制作用增强。然而，未发现血浆硝酸盐或cGMP与B-Pb或P-Pb浓度之间存在显著相关性（所有P > 0.05）。这些发现表明铅暴露对NO生成有显著抑制作用，并为可能涉及铅暴露与心血管风险增加之间关联的生物学机制提供了临床证据。
