Lead alleviates cadmium hepatotoxicity by remodeling its coordination environment: A combined XAFS and DFT study

Cadmium (Cd) and lead (Pb) frequently co-occur in contaminated environments, yet the toxicological interaction between them remains unclear. Here, we established a rat model of combined Cd and Pb exposure and used FTIR, synchrotron XAFS, and DFT calculations to examine the coordination mechanism underlying Pb-mediated modulation of Cd hepatotoxicity. Pb co-exposure significantly attenuated Cd-induced liver injury, as shown by reduced serum ALT, ALP, and GGT levels and alleviated histopathological damage. Spectroscopic and computational analyses revealed that Pb alters the local coordination environment of Cd by competing for oxygen-containing ligands in GSH and bridging sulfur atoms in MT, thereby weakening Cd-S interactions and promoting Cd redistribution from LCF-derived free Cd²⁺ fraction to GSH-/MT-bound forms. Pb co-exposure alleviates Cd-induced hepatotoxicity, and this effect is associated with changes in Cd coordination chemistry, underscoring the importance of metal speciation in assessing mixed-metal exposure risk.