Association of miRNA-31 & miRNA 192 with Nrf2/NF-κB Biomarkers in Occupational Lead Toxicity: A Cross-Sectional...

Lead (Pb) exposure is a global health threat characterized by oxidative stress. While Nrf2 and NF-κB pathways are known mediators of systemic toxicity, the epigenetic modulation of these defences via microRNAs (miRNAs) in human cohorts remains to be fully elucidated. This study investigates the association between blood lead levels (BLL) and a potential molecular signalling involving miRNA-31, miRNA-192, Nrf2, and NF-κB. In this cross-sectional study, 80 occupationally lead-exposed healthy workers and 80 age-gender matched healthy controls were enrolled. BLL was estimated using Graphite Furnace Atomic Absorption Spectrometry (GFAAS). Relative expressions of miRNA-31, Nrf2, and NF-κB were quantified via RT-PCR, while serum protein levels were measured using commercially available sandwich ELISA kits. The exposed group exhibited significantly higher median BLL compared to controls (p < 0.001). A significant downregulation was observed in Nrf2 mRNA expression (fold change 0.53) and serum protein levels (p < 0.001) in occupationally exposed group. Additionally, the inflammatory transcription factor, NF-κB also showed an increasing trend and a slight positive correlation with BLL. Among miRNAs, miRNA-31 was significantly upregulated (fold change 3.95). In multivariable linear regression, miRNA-31 showed a significant inverse association with Nrf2 expression in the unadjusted model ([Formula: see text], [Formula: see text]). However, after adjusting for blood lead levels, the effect of [Formula: see text] was substantially reduced, while BLL remained significantly and inversely associated with Nrf2 expression ([Formula: see text], [Formula: see text]) Occupational lead exposure is accompanied by systemic miRNA-31 induction and reduced Nrf2 expression. These observational results suggest that blood lead levels exert a primary influence on Nrf2 suppression, offering hypothesis-generating insights into early epigenetic and redox responses during lead toxicity.