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

Gomez Pellin, Maria Cruz; Linares-Ruiz, Eduardo; Esteban, Javier; Salcedo-Bellido, Inmaculada; Çakmak, Gonca; Velasco García, María Eugenia; Barril, Jose; Galbán-Velázquez, Suylen; Pérez-Díaz, Celia; Pérez-Carrascosa, Francisco M.; Vrhovnik, Petra; Fiket, Željka; Pellín, María de la Cruz; Arrebola, Juan P. (2025) Adipose tissue cadmium concentrations as potential determinants of serum PON1 status in an adult cohort from Southern Spain. Environmental Toxicology and Pharmacology, 120 . ISSN 1382-6689

PDF - Published Version - article Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (23MB)

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 PON1Q192R 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 PON1Q192R 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 PON1Q192R phenotype. Additionally, benchmark dose (BMD) modelling was performed. Higher adipose tissue Cd concentrations were associated with lower PON1 activities. PON1Q192R 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 mgCd/kgadipose-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.

Item Type:	Article
Uncontrolled Keywords:	Cadmium; Adipose tissue; PON1; PON1Q192R phenotype; Atherosclerosis; Benchmark dose modelling
Subjects:	NATURAL SCIENCES > Interdisciplinary Natural Sciences > Environmental Science BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Pharmacology
Divisions:	Division for Marine and Enviromental Research
Depositing User:	Lorena Palameta
Date Deposited:	09 Oct 2025 08:11
URI:	http://fulir.irb.hr/id/eprint/10049
DOI:	10.1016/j.etap.2025.104827

Actions (login required)

View Item