Anemia and Toxic Metals Exposure in the Amazon: Identification of mechanisms and biomarkers using omics tools

• Grant number: 25/09756-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Fernando Barbosa Júnior
• Grantee: Flora Troina Maraslis
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/24069-3 - ReSEARCH: Recognizing Signatures of the Exposome to Anticipate the Risks for a Continuous Health, AP.TEM

Abstract

The dietary and lifestyle habits of riverside communities in the Amazon can pose significant risks to individual health. One example is the high consumption of fish - the main source of animal protein for these populations - which results in chronic exposure to high concentrations of mercury (Hg). In addition, the presence of lead (Pb) has been identified in cassava flour, a widely consumed food traditionally prepared by hand.Both metals have a high affinity for thiol groups, which can compromise the activity of proteins sensitive to the redox state, inducing oxidative stress. Enzymes vulnerable to this interaction include those involved in the heme biosynthesis pathway, such as delta-aminolevulinic acid dehydratase (ALAD), which contains cysteine residues in its structure. Inhibition of ALAD by Pb and Hg can aggravate anemia, especially when associated with other predisposing factors.The study of genetic polymorphisms allows the assessment of individual susceptibility to metal toxicity, while the integrated use of omics technologies - such as transcriptomics and metabolomics - enables the in-depth characterization of the metabolic pathways involved, contributing to the understanding of the molecular mechanisms of the disease and improving health. In this context, the present study aims to investigate the association between exposure to Hg and Pb and the occurrence of anemia, through the integrated analysis of genomic (polymorphisms), transcriptomic and metabolomic data. Four hundred individuals living in riverside communities in the Amazon will participate in the study, who will answer questionnaires about health and eating habits, in addition to providing anthropometric measurements and biological samples (blood and urine).Hemoglobin concentration will be determined by spectrophotometry, while Pb, Hg, selenium (Se) and iron (Fe) levels will be quantified by inductively coupled plasma mass spectrometry (ICP-MS). Genotyping will be performed by real-time polymerase chain reaction (qPCR) using the TaqMan methodology. Transcriptome analysis will be conducted using the GeneChip array, and the metabolome will be evaluated by mass spectrometry and nuclear magnetic resonance (NMR).The data obtained will be initially analyzed by descriptive statistics and subsequently subjected to multivariate analyses. Specialized software will be used to integrate the omics data, with the aim of identifying relevant metabolic pathways, potential biomarkers and genetic factors associated with susceptibility and increased risk for anemia related to exposure to the toxic metals Hg and Pb.