Spatial Land Use Dynamics Driving Molecular Stress and Unacceptable Human Health Risks in Standardized Catfish Aquaculture Systems

Aquaculture sustainability in rapidly urbanizing regions is increasingly threatened by heavy metal contamination originating from complex anthropogenic land-use patterns. This study used an integrated model to evaluate the molecular-to-human health continuum in hybrid catfish (Clarias gariepinus × Clarias macrocephalus) sourced from Pathum Thani, Thailand’s primary aquaculture hub. We integrated geospatial land-use data with heavy-metal quantification, oxidative-stress biomarkers, and transcriptional profiling to assess how canal-specific water quality modulates fish health and consumer risk. The results revealed significant spatial heterogeneity in metal concentrations, corresponding to the province’s 27% urban–industrial land-use footprint. While water quality generally met regulatory limits, a pronounced aqueous–biotic discrepancy, “bioaccumulation paradox” was identified at certain sites, where muscle and hepatic tissues exhibited lead (Pb), chromium (Cr), and nickel (Ni) levels that substantially exceeded international safety standards. Biochemical and molecular analyses provided functional evidence of physiological distress, specifically significantly elevated malondialdehyde (MDA) levels, and the transcriptional modulation of cat, cyp1a, gpx, met, tnf, and star genes indicated that chronic metal exposure overwhelmed antioxidant defenses and induced potential endocrine disruption. Moreover, human health risk assessments revealed that the hazard index (HI) and target cancer risk (TR) exceeded unacceptable thresholds at multiple hotspots, indicating that Cr is a primary carcinogenic driver. These findings highlight a “GAP Paradox,” where farm-level certifications are insufficient to mitigate risks posed by the surrounding canal network. This study presents vital evidence-based risk profiles that necessitate a transition to a spatially based regulatory framework, incorporating geospatial land-use monitoring into national food safety policies to protect both aquaculture viability and public health.