In vivo and in silico approach in revealing the influence of lead (Pb) on thyroid gland function

Abstract

The purpose of this study was to examine the impact of low doses of lead (Pb) on levels of thyroid hormones (T3, T4, FT3, and FT4) and thyroid-related antibodies (anti-Tg and anti-TPO) in the rat model, as well as genes that are related to Pb and thyroid function, relationships between genes, biological processes, molecular processes, and pathways using an in silico approach. Male rats were randomized into seven groups (n = 42), one control group and six groups that received a range of Pb doses: 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg body weight (b.w.). Dose-response modelling was performed by PROAST software using model averaging method. The Comparative Toxicogenomics Database, GeneMANIA server, and ToppGene Suite portal were used as the main bioinformatic tools in this analysis. The results of our study have shown that low Pb doses induced elevation of thyroid hormones (T4, FT4, and TSH) in rats after subacute exposure, while had no impact on T3, FT3, anti-TPO, and anti-Tg, indicating hyperthyroidism. Dose-dependent effects were increases in T4 and FT4, with the lowest benchmark dose derived for FT4 levels. In silico toxicogenomic data analysis showed that the main molecular pathways/process related to Pb-induced hyperthyroidism are connected with 14 genes involved in antioxidant defense and Se-dependent processes. The results presented here may be useful in further investigation of the health impacts of low-level Pb exposure on thyroid function and endocrine disruption effects.