Exploring specific biomarkers regarding neurobehavioral toxicity of lead dioxide nanoparticles in medaka fish in different water matrices

Abstract

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.