Transcriptome analysis unveils the mechanisms of oxidative stress, immunotoxicity and neurotoxicity induced by benzotriazole UV stabilizer-328 in zebrafish embryos
Xinlu Yang, Yijing Gan, Menghuan Zhang, Shaolin Xie, Mingfu Lin, Lixiang Zhong, Mengke Song, Jun Wang, Yumei Huang
Abstract
As an emerging pollutant, ultraviolet stabilizer-328 (UV-328) has been frequently detected in aquatic environments and attracted great attention. Nevertheless, the toxicity and mechanisms of UV-328 to aquatic organisms are still not fully understood. In particular, the immunotoxicity and neurotoxicity of UV-328 to aquatic organisms and their mechanisms have not been reported yet. In this experiment, the developmental toxicity, oxidative stress, apoptosis, immunotoxicity and neurotoxicity in zebrafish embryos exposed to UV-328 with concentrations of 0.01, 0.1, 1, 10 and 100 µg/L for 120 h were studied. By measuring the growth and developmental indices, production of ROS, enzyme activities, MDA content and expression of genes related to oxidative, immune and nerve, and histopathological analysis, it was found that UV-328 had developmental toxicity to zebrafish larvae, and could induce oxidative stress, immunotoxicity and neurotoxicity to zebrafish larvae even at environmental concentrations with concentration-dependent effects. Moreover, the results of transcriptome analysis and qRT-PCR validation suggested that immune and nerve disorders were caused by UV-328 in zebrafish larvae through regulating the RIG-I-like receptor signaling pathway and neuroactive ligand-receptor interaction, respectively. In addition, transcriptome analysis further revealed that UV-328 could mediate the RIG-I to induce oxidative stress through p38-MAPK/p53 signaling pathway, leading to apoptosis and oxidative damage. In addition, the p38-MAPK signaling pathway enhanced ROS production and activated inflammatory cytokines to induce immunotoxicity. The results of the present work provided important information for understanding the toxicity of UV-328 to aquatic organisms and evaluating its ecological risk in aquatic environment. • A first study on the immunotoxicity and neurotoxicity of UV-328 to organisms. • UV-328 would inhibit the development of zebrafish embryos/larvae. • Immunotoxicity was induced in zebrafish via RIG-I-like receptor signaling pathway. • Neurotoxicity was induced in zebrafish via neuroactive ligand-receptor interaction. • Oxidative stress and apoptosis were caused via p38-MAPK/p53 signaling pathway.