Antioxidant capacity and esterase activity of serum albumin toward interaction with HPPD inhibitors: Multi-spectral and computational studies

Sulcotrione and mesotrione are novel plant 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors. The overuse of these herbicides can bring the risk to environment and human. In this study, multispectral methods, density functional theory (DFT) calculations, and molecular docking techniques were used to investigate how sulcotrione and mesotrione interact with human serum albumin (HSA) and bovine serum albumin (BSA). The results revealed that both herbicides quenched the endogenous fluorescence of HSA/BSA through a static quenching mechanism. Circular dichroism (CD), Fourier Transform Infrared (FTIR), synchronous fluorescence, and three-dimensional (3D) fluorescence spectra demonstrated that sulcotrione and mesotrione induced conformational and secondary structural changes in HSA and BSA. Thermodynamic studies indicated that hydrogen bonding and van der Waals forces were the primary driving forces behind these interactions. Additionally, both compounds enhanced the esterase activity and antioxidant capacity of HSA and BSA while altering amino acid residues. The in vivo toxicity test and ROS levels results of zebrafish also showed that the toxicity of mesotrione was higher than that of sulcotrione. This study provides critical insights into the potential health risks posed by HPPD inhibitors to humans and mammals, emphasizing the need for further safety evaluations.