Synergistic hepatotoxicity by cadmium and chlorpyrifos: Disordered hepatic lipid homeostasis

Due to its extensive application, chlorpyrifos (CPF) has contaminated a diverse range of environmental substrates, fruits and vegetables. A number of studies have suggested that CPF may incur adverse effects on human health, including neurotoxicity, hepatotoxicity and endocrine disruption. Additionally, cadmium (Cd) is one of the most prevalent environmental heavy metals, as a result of considerable use in a wide spectrum of industrial fields. Exposure to Cd can cause several lesions in various organs, including the liver, kidneys and lungs. CPF and Cd often co-exist in the environment, food and crops, however, their joint exposure and potential synergistic toxicity are largely neglected and unrecognized. Our previous study characterized an interaction between CPF and Cd, which may occur via bonding between Cd2+ and the nitrogen atom in the pyridine ring of CPF, or the chelation between one Cd2+ and two CPF molecules. Our previous study also identified increased hepatotoxicity induced by CPF and Cd together compared with the individual compounds. In the present study, the effects of the concomitant exposure of CPF and Cd on lipid metabolism in hepatocytes was investigated. The results demonstrated an accumulation of lipids in hepatocytes, induced by the CPF and Cd complex, which was fundamentally distinct from its parental chemicals. Notably, the molecular mechanism by which the CPF-Cd complex significantly induced hepatic lipogenesis was revealed, elevating the concentrations of sterol regulatory element-binding protein-1 and fatty acid synthase. These findings pave the way for future studies in recognizing synergistic biological effects between pollutants.