Epigenetic alterations and neurotoxic effects in Amazonian riverside populations co-exposed to lead and methylmercury and potential modulator effect of selenium and selenoenzyme genotypes

• Grant number: 23/00226-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2023
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Fernando Barbosa Júnior
• Grantee: Marília Ladeira de Araújo
• 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

Riverside communities in the Amazon consume fish daily, serving as the main source of protein, thus increasing the risk of exposure to MeHg. However, Amazonian populations are also exposed to lead (Pb) through the consumption of cassava flour. The study population demonstrates a high level of Selenium (Se) in blood samples, without demonstrating intoxication by the element. Thus, studies are showing the role of Se in the brain and in neurodegenerative diseases. Selenoprotein polymorphisms can show different modulations in the Se status response in individuals; In this context, the present project aims to evaluate the potential effect of Se through polymorphisms in the attenuation of neurotoxic effects, as well as on the epigenetic status in the Amazonian riverside population co-exposed to Pb and MeHg. The quantifications of Hg, Pb and Se will be determined in blood, plasma and urine, by LC-ICP-MS. The expressions of miRNAs will be performed by TaqMan assays (RT-qPCR). Histone expression will be performed in peripheral blood samples using the buffy coat technique and, finally, genotyping will be performed using the TaqMan SNP Genotyping Assays system (Applied Biosystems), using the cycling conditions determined by the manufacturer. Advanced statistical models will be used so that the results obtained help in a better understanding of the molecular and genetic toxicological mechanisms involved in the co-exposure to metals, and the possible protective role of Se on the deleterious neurological effects measured in this population. (AU)