Contents lists available at ScienceDirect Toxicology and Applied Pharmacology journal homepage: www.elsevier.com/locate/taap Natriuretic peptides and echocardiographic parameters in Mexican children environmentally exposed to arsenic José M. Torres-Arellano a,1 , Citlalli Osorio-Yáñez b,1 , Luz C. Sánchez-Peña a , Julio C. Ayllon-Vergara c , Laura Arreola-Mendoza d , Guadalupe Aguilar-Madrid e , Luz M. Del Razo a, ⁎ a Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, Mexico b Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico c Servicio de Cardiología del Hospital General de México, Ciudad de México, Mexico d Departamento de Biociencias e Ingenieria, Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y Desarrollo del Instituto Politécnico Nacional, Ciudad de México, Mexico e Dirección de Investigación y de Posgrado, Claustro Universitario de Chihuahua, Chihuahua, Mexico ARTICLE INFO Keywords: B-Type natriuretic peptide Arsenic exposure Echocardiographic evaluation Children ABSTRACT Background: Arsenic exposure is associated with cardiovascular risk in adults; however, few epidemiologic studies have evaluated biomarkers of cardiovascular risk in children who are environmentally exposed to ar- senic. Objective: The aim of this study was to assess the associations between urinary arsenic, plasma natriuretic peptides and echocardiographic parameters in Mexican children exposed to arsenic through the drinking water. Methods: We conducted a cross-sectional study with 192 children (3–8 years old) from Zimapan, Hidalgo, Mexico. B-type natriuretic peptide (BNP), NT-proBNP and atrial natriuretic peptide (ANP) were measured by ELISA, urinary arsenic concentration (UeAs) were measured via by hydride generation-cryotrapping-atomic absorption spectrometry, and cardiac parameters were measured by echocardiography. Results: The median plasma concentrations of ANP, BNP and NT-proBNP were 36.9 ng/mL, 49.7 pg/mL, and 226.1 pg/mL, respectively. Using multivariable models, a dose-response relationship was observed between BNP concentrations and UeAs tertiles (< 47 ng/mL: reference, 47–72 ng/mL: 48.7 pg/mL, > 72 ng/mL: 52.2 pg/mL, P-trend = 0.020). BNP concentrations also increased with increasing U-tAs as continuous variables (0.43 pg/mL increase per 1 ng/mL increase of U-tAs; P-Value = 0.008). Additionally, BNP was positively associated with arsenic methylated metabolites (U-MAs and U-DMAs). On the other hand, BNP was inversely related to relative wall thickness (RWT). No associations were found for other cardiac parameters. Finally, neither ANP nor NT- proBNP were significantly related to arsenic exposure or echocardiographic parameters. Conclusions: In this study, we showed associations between plasma BNP and arsenic exposure. Our results support the importance of reducing childhood arsenic exposure, which may have cardiovascular effects early in life. 1. Introduction Inorganic arsenic is present in drinking water at high concentrations in many countries around the world including India, Chile, Mexico, Taiwan, and the United States. The cardiovascular effects of arsenic previously described in adults include hypertension (Hall et al., 2017), QT interval prolongation (Mumford et al., 2007; Wang et al., 2007), atherosclerosis (Wang et al., 2002), cardiac ischemia and hypertrophy (Ahmad et al., 2006), among others; however, few epidemiologic stu- dies have evaluated cardiovascular risk biomarkers in relation to ar- senic exposure. Natriuretic peptides are endogenous hormones secreted by cardiac https://doi.org/10.1016/j.taap.2020.115164 Received 14 April 2020; Received in revised form 18 July 2020; Accepted 26 July 2020 ⁎ Corresponding author at: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Ciudad de México, 07360, Mexico. E-mail address: Ldelrazo@cinvestav.mx (L.M. Del Razo). 1 Authors contributed equally. Toxicology and Applied Pharmacology 403 (2020) 115164 Available online 29 July 2020 0041-008X/ © 2020 Elsevier Inc. All rights reserved. T