Myelin toxicity of chlorhexidine in zebrafish larvae

Abstract

Background Chlorhexidine gluconate (CHG) is a topical antiseptic solution recommended for skin preparation before central venous catheter placement and maintenance in adults and children. Although CHG is not recommended for use in children aged <2 months owing to limited safety data, it is commonly used in neonatal intensive care units worldwide. We used zebrafish model to verify the effects of early-life exposure to CHG on the developing nervous system, highlighting its impact on oligodendrocyte development and myelination. Methods Zebrafish embryos were exposed to different concentrations of CHG from 4 h post fertilization to examine developmental toxicity. The hatching rate, mortality, and malformation of the embryos/larvae were monitored. Oligodendrocyte lineage in transgenic zebrafish embryos was used to investigate defects in oligodendrocytes and myelin. Myelin structure, locomotor behavior, and expression levels of genes involved in myelination were investigated. Results Exposure to CHG significantly induced oligodendrocyte defects in the central nervous system, delayed myelination, and locomotor alterations. Ultra-microstructural changes with splitting and fluid-accumulated vacuoles between the myelin sheaths were found. Embryonic exposure to CHG decreased myelination, in association with downregulated mbpa, plp1b, and scrt2 gene expression. Conclusion Our results suggest that CHG has a potential for myelin toxicity in the developing brain. Impact To date, the neurodevelopmental toxicity of chlorhexidine gluconate (CHG) exposure on the developing brains of infants remains unknown. We demonstrated that CHG exposure to zebrafish larvae resulted in significant defects in oligodendrocytes and myelin sheaths. These CHG-exposed zebrafish larvae exhibited structural changes and locomotor alterations. Given the increased CHG use in neonates, this study is the first to identify the risk of early-life CHG exposure on the developing nervous system.