Developmental neurotoxicity induced by glutaraldehyde in neuron/astrocyte co-cultured cells and zebrafish

Abstract

The genotoxicity, development toxicity, carcinogenicity, and acute or chronic toxic effects of glutaraldehyde (GA), particularly during occupational exposure through its use as a fixative, disinfectant, and preservative, are well-documented but its effects on neurotoxicity have not been investigated. We performed in vitro and in vivo studies to examine the developmental neurotoxicity (DNT) of GA. Neurite outgrowth was examined in an in vitro co-culture model consisting of SH-SY5Y human neuroblastoma cells and human astrocytes. Cell Counting Kit-8, lactate dehydrogenase assay, and high-content screening revealed that GA significantly inhibited neurite outgrowth at non-cytotoxic concentration. Further studies showed that GA upregulated the mRNA expression of the astrocyte markers GFAP and S100β and downregulated the expression of the neurodevelopmental genes Nestin, βIII-tubulin, GAP43, and MAP2. Furthermore, in vivo zebrafish embryo toxicity tests explored the effects of GA on neural morphogenesis. GA adversely affected the early development of zebrafish embryos, resulting in decreased survival, irregular hatching, and reduced heart rate in a time- and concentration-dependent manner. Furthermore, the width of the brain and spinal cord was reduced, and the myelination of Schwann cells and oligodendrocytes was decreased by GA in transgenic zebrafish lines. These data suggest that GAs have potential DNT in vitro and in vivo, highlighting the need for caution regarding the neurotoxicity of GA.