Adipose tissue cadmium concentrations as potential determinants of serum PON1 status in an adult cohort from Southern Spain

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2025-09-25 DOI:10.1016/j.etap.2025.104827

Maria Cruz Gomez Pellin , Eduardo Linares-Ruiz , Javier Esteban , Inmaculada Salcedo-Bellido , Gonca Çakmak , María Eugenia Velasco García , Jose Barril , Suylen Galbán-Velázquez , Celia Pérez-Díaz , Francisco M. Pérez-Carrascosa , Petra Vrhovnik , Željka Fiket , María de la Cruz Pellín , Juan P. Arrebola

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引用次数: 0

Abstract

Paraoxonase 1 (PON1) is an antiatherogenic enzyme inhibited by environmental stressors such as cadmium (Cd). Thus, this human study aimed to assess (1) the associations between adipose tissue Cd concentrations and serum PON1 status and (2) the influence of the PON1_Q192R phenotype on the susceptibility of PON1 status to Cd. As a continuation from previous work, a subsample from the GraMo cohort (Granada, Spain) was studied. Three PON1 activities using non-organophosphorous substrates {PALS (phenyl acetate in the absence of NaCl), PAHS (phenyl acetate in 2 M NaCl) and CMPA [4-(chloromethyl)phenyl acetate]} were assayed in serum (n = 296) to obtain the three functional PON1_Q192R phenotypes (QQ, QR and RR). Complementarily, Cd concentrations in adipose tissue (n = 226) and information on socio-demographic characteristics, lifestyle, diet and health status acquired by face-to-face interviews were available. The associations between PON1 activities in serum and Cd concentrations in adipose tissue (subset of n = 138) were explored by using linear regression models, which were adjusted for sex, alcohol consumption and PON1_Q192R phenotype. Additionally, benchmark dose (BMD) modelling was performed. Higher adipose tissue Cd concentrations were associated with lower PON1 activities. PON1_Q192R specific susceptibility to Cd increased in the order QQ < QR < RR. The Cd BMD ranges for an averaged subject were 0.002–0.016 and 0.046–0.115 mg_Cd/kg_{adipose-tissue} for RR and QR, respectively. For QQ cases, the BMD were higher than the Cd concentrations found in adipose tissue. These results suggest that part of the increased susceptibility of the RR cases to cardiovascular diseases might putatively be mediated by its higher sensitivity to Cd, with adipose tissue Cd levels serving as a biomarker of chronic exposure.

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脂肪组织镉浓度作为西班牙南部成人队列血清PON1状态的潜在决定因素

对氧磷酶1 （PON1）是一种抗动脉粥样硬化酶，可被环境应激因子如镉（Cd）抑制。因此，这项人体研究旨在评估(1)脂肪组织Cd浓度与血清PON1状态之间的关系，(2)PON1Q192R表型对PON1状态对Cd易感性的影响。作为先前工作的延续，研究了来自GraMo队列（西班牙格拉纳达）的子样本。用非有机磷底物{PALS（无NaCl条件下的乙酸苯酯）、PAHS （2M NaCl条件下的乙酸苯酯）和CMPA[4-（氯甲基）乙酸苯酯]}}测定3种PON1在血清中的活性（n = 296），得到3种功能性PON1Q192R表型（QQ、QR和RR）。此外，还可获得脂肪组织中的Cd浓度（n = 226）以及通过面对面访谈获得的有关社会人口特征、生活方式、饮食和健康状况的信息。利用线性回归模型，对性别、酒精摄入量和PON1Q192R表型进行了调整，探讨了血清中PON1活性与脂肪组织中Cd浓度（n = 138个亚组）之间的关系。此外，进行基准剂量（BMD）建模。较高的脂肪组织Cd浓度与较低的PON1活性相关。PON1Q192R对Cd的特异性敏感性以QQ < QR < RR的顺序递增。RR和QR的Cd骨密度平均值分别为0.002-0.016 mg /kg -tissue和0.046-0.115 mg /kg -tissue。在QQ病例中，骨密度高于脂肪组织中的Cd浓度。这些结果表明，RR病例对心血管疾病易感性增加的部分可能是由其对Cd的更高敏感性介导的，脂肪组织Cd水平可作为慢性暴露的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.