Mu-Xuan Wang, Nan Chen, Mo Chen, Xian-Yi Zhang, Xu Guo, Shu-Tao Sun, Mohamed A Farag, Fei Dong, Ning-Yang Li, Chao Liu
Recently, pesticide residues have become a serious environmental hazard due to the widespread employment of pesticides in agricultural production. With the continuous accumulation of pesticide in vivo, liver injury caused by pesticide metabolism has become a rapidly developing disease. Although pesticide-mediated liver injury (PMLI) has attracted extensive attention, its diagnosis and treatment still face serious challenges. Previous studies have indicated that PMLI is closely related to oxidative stress caused by pesticides, in which the abnormal level of hydrogen peroxide (H2O2) is a critical biomarker. Consequently, monitoring the H2O2 level is essential for the early diagnosis and efficacy assessment in PMLI. Based on the advantages of near-infrared fluorescence imaging technology, this study designed and synthesized a novel fluorescence probe (DOA-1) to real-time image H2O2 in PMLI. DOA-1 exhibited excellent imaging capacity toward exogenous and endogenous H2O2 in living cells and zebrafish models, with high sensitivity and selectivity. At the same time, DOA-1 was successfully applied to image H2O2 in pesticide-induced cells, zebrafish and mouse models, thereby confirming that oxidative stress was the main factor causing liver injury by pesticides. Furthermore, DOA-1 facilitated the efficacy assessment of flavonoid compounds, identifying that puerarin could effectively alleviate oxidative stress caused by pesticides. Molecular mechanism studies revealed that puerarin could ameliorate lipid peroxidation and fibrosis in PMLI by regulating Keap1-Nrf2 signaling pathway. Overall, this study provides a novel tool for diagnosing and assessing the impact of oxidative stress caused by pesticide residues on liver function.