Exploring specific biomarkers regarding neurobehavioral toxicity of lead dioxide nanoparticles in medaka fish in...

Nano-scale lead dioxide (nPbO₂) is an industrial metal oxide nanoparticle that can be also formed as a corrosion by-product from chlorination of Pb-containing plumbing materials. nPbO₂ governs release of toxic lead ion in drinking water and receiving organisms; however, its modes of toxic action regarding neurobehavioral toxicity remain unclear. This study evaluated the toxicity mechanism of nPbO₂ (10 and 20 mg/L) versus its released Pb(II)_aq (100 μg/L) in terms of aqueous chemistry, bioavailability and neurobehavioral toxicity to medaka fish in different water matrices. In very hard water (VHW), dissolved salts enhanced the aggregation and sedimentation of nPbO₂, resulting in higher bioavailability and altered locomotion of treated fish than those fish exposed to nPbO₂ in soft water with humic acid (SW + HA). Transcriptomic results identified six differentially expressed genes with greater altered expression with nPbO₂ than the control or Pb(II)_aq exposure. With VHW exposure, nPbO₂ caused greater altered expression of genes involved in cell adhesion (nlgn1 and epd), cell cytoskeleton (α1-tubulin), and relevant apoptosis (c-fos, birc5.1-a and casp3), as compared with SW + HA or Pb(II)_aq exposure. This study provides novel molecular mechanistic insights into the neurobehavioral nanotoxicity using nPbO₂ and medaka fish as surrogates, suggesting nPbO₂ promotes neurobehavioral dysfunction, leading to adverse outcomes from gene alteration to the organismal level. The identified biomarkers responded specifically to the nPbO₂-induced neurotoxicity in different water matrices can be used for evaluating toxicity risks of small metal oxide particulates on human or aquatic life under environmentally relevant exposures.