Solvothermal transformation of antibiotics and hidden toxic risks during food cooking.

The chemical fate and toxicological evolution of food antibiotic residues in oil and water, the most common liquid media in food preparation under solvothermal conditions, remain largely unexplored. In this study, we investigate the solvothermal transformation of sulfamethoxazole and evaluate the nephrotoxicity of its solvothermal transformation products (STPs). Heated oil acts as a highly reactive medium in which long-chain fatty acid radicals drive 99.7% conversion, while only 2.6% transformation occurs in water. Oil-related STPs exhibit pronounced secondary toxicity in human kidney cells, leading to cytotoxicity through oxidative stress. This stress response is characterized by increased lipid synthesis and suppressed lipolysis, which synergistically activate the nuclear factor erythroid-derived factor 2-related factor 2 signaling pathway. The resulting metabolic reprogramming ultimately causes severe disruption of cellular lipid homeostasis. Collectively, these findings highlight the need to consider the potential health risks associated with chronic, low-level dietary exposure to antibiotic-derived STPs formed under oil-heating conditions.