Dinotefuran exposure induces immunotoxicity in zebrafish embryos

Abstract

As a typical neonicotinoid insecticide, dinotefuran (DIN) has immunotoxicity, but its immunotoxicity effects on aquatic organisms and its molecular mechanisms are not known. In this study, zebrafish embryos were used as model to reveal its immunotoxicity and its mechanism from the perspective of inflammatory response. Zebrafish larvae were exposed to DIN at environmentally relevant concentrations (0, 2, 200, and 2000 mg/L) for 120 h, followed by comprehensive analyses of immune cell populations, immune marker activities, oxidative stress levels, and gene expression profiles. The results showed that the number of neutrophils and macrophages, two types of innate immune cells, was significantly reduced, and the activities of the immune markers, lysozyme (LYS), immunoglobulin M (IgM), and complement protein C3, were significantly inhibited. The level of oxidative stress in zebrafish larvae was significantly elevated and antioxidant enzyme activities were markedly inhibited in a dose-dependent manner after exposure to DIN. In this case, pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were also abnormally expressed, and the expression levels of the genes related to the NF-κB pathway and the JNK-STAT pathway, tlr4a, myd88, nf-κb p65, jak1, jak2, and stat3, were elevated. The expression levels of genes related to the antioxidant signaling pathway Nrf2-keap1 signaling pathway were suppressed. Taken together, our results suggest that DIN exposure causes damage to the immune system of zebrafish embryos-larvae, generating oxidative stress and inflammatory responses that lead to immunotoxicity.