Almeida Lopes Ana Carolina Bertinde, Urbano Mariana Ragassi, Souza-Nogueira André de, Oliveira-Paula Gustavo H, Michelin Ana Paula, Carvalho Maria de Fátima H, Camargo Alissana Ester Iakmiu, Peixe Tiago Severo, Cabrera Marcos Aparecido Sarria, Paoliello Monica Maria Bastos
Graduate Program in Public Health, Center of Health Sciences, State University of Londrina, Londrina, PR 86038-350, Brazil.
Department of Statistics, State University of Londrina, Londrina, PR 86057-970, Brazil.
Environ Res. 2017 Jul;156:674-682. doi: 10.1016/j.envres.2017.04.036. Epub 2017 May 5.
Metal exposure is associated with increased oxidative stress (OS), which is considered an underlying mechanism of metal-induced toxicity. Malondialdehyde (MDA) is a final product of lipid peroxidation, and it has been extensively used to evaluate metal-induced OS. Pro-oxidant effects produced by metals can be mitigated by paraoxonase 1 (PON1), an antioxidant enzyme known to prevent cardiovascular disease and atherosclerosis. Among other factors, the Q192R polymorphism and the exposure to heavy metals have been known to alter PON1 activity. Here, we evaluated the association of blood lead (Pb), cadmium (Cd) and mercury (Hg) levels with PON1 activity, and with MDA concentrations in a randomly selected sample of Brazilian adults aged 40 years or older, living in an urban area in Southern Brazil. A total of 889 subjects were evaluated for blood Pb and Cd levels, and 832 were tested for Hg. Geometric mean of blood Pb, Cd and Hg was 1.93μg/dL, 0.06μg/L and 1.40μg/L, respectively. PON1 activity was significantly different among various genotypes: QQ (PON1=121.4U/mL), QR (PON1=87.5U/mL), and RR (PON1=55.2U/mL), p<0.001. PON1 genotypes were associated only with Cd blood levels. Those with QR genotype had Cd concentrations higher (0.07μg/L) than those with the RR genotype (0.04μg/L) with p=0.034. However, PON1 activity was not significantly associated with metal concentrations. Cluster analysis showed that men who reported to be current smokers and drinkers with higher blood Pb and Cd levels, had significantly lower PON1 activity than non-smokers or -drinkers, and women with lower Pb and Cd levels. RR genotype carriers had lower PON1 activity than those with the QR genotype, and had higher levels of Pb and Cd compared with other genotype carriers. For blood Hg, no association with PON1 activity or genotype was noted. We found low levels of Pb, Cd and Hg in environmentally exposed Brazilian adults. Cd concentrations were increased in subjects with QR genotype. Those with RR genotype had lower PON1 activity and higher levels of Pb and Cd than other genotype carriers. The results of cluster analysis suggested that smoking status exerts a significant influence on PON1 activity. Other studies with environmentally exposed populations are required to further clarify whether low blood levels of metals influence OS biomarkers.
金属暴露与氧化应激(OS)增加有关,氧化应激被认为是金属诱导毒性的潜在机制。丙二醛(MDA)是脂质过氧化的终产物,已被广泛用于评估金属诱导的氧化应激。对氧磷酶1(PON1)是一种已知可预防心血管疾病和动脉粥样硬化的抗氧化酶,它可以减轻金属产生的促氧化作用。在其他因素中,已知Q192R多态性和重金属暴露会改变PON1活性。在此,我们评估了巴西巴西南部城市地区40岁及以上随机抽取的成年人样本中血铅(Pb)、镉(Cd)和汞(Hg)水平与PON1活性以及MDA浓度之间的关联。共对889名受试者进行了血铅和镉水平评估,对832名受试者进行了汞检测。血铅、镉和汞的几何平均值分别为1.93μg/dL、0.06μg/L和1.40μg/L。不同基因型的PON1活性存在显著差异:QQ型(PON1 = 121.4U/mL)、QR型(PON1 = 87.5U/mL)和RR型(PON1 = 55.2U/mL),p<0.001。PON1基因型仅与血镉水平相关。QR基因型者的镉浓度(0.07μg/L)高于RR基因型者(0.04μg/L),p = 0.034。然而,PON1活性与金属浓度无显著关联。聚类分析表明,报告为当前吸烟者和饮酒者且血铅和镉水平较高的男性,其PON1活性显著低于非吸烟者或非饮酒者以及血铅和镉水平较低的女性。RR基因型携带者的PON1活性低于QR基因型者,且与其他基因型携带者相比,其铅和镉水平更高。对于血汞,未发现与PON1活性或基因型有关联。我们发现环境暴露的巴西成年人中铅、镉和汞水平较低。QR基因型受试者的镉浓度升高。RR基因型者的PON1活性较低,且铅和镉水平高于其他基因型携带者。聚类分析结果表明吸烟状况对PON1活性有显著影响。需要对环境暴露人群进行其他研究,以进一步阐明低血金属水平是否会影响氧化应激生物标志物。