TY - JOUR AU - Karimov, D. O. AU - Ryabova, Yu. V. AU - Repina, E. F. AU - Valova, Ya. V. AU - Gizatullina, A. A. AU - Yakupova, T. G. AU - Smolyankin, D. A. AU - Khmel, O. A. AU - Kurilov, M. V. T1 - Chronic Stress Enhances Hepatotoxic Effects of Sorbic and Benzoic Acids in a Rat Model JO - Journal of Stress Physiology & Biochemistry Y1 - 2025/december VL - 21 IS - 4 SP - 32 EP - 44 UR - http://www.jspb.ru/issues/2025/N4/JSPB_2025_4_32-44.pdf KW - chronic stress KW - food preservatives KW - liver KW - gene expression KW - Sod1 KW - Hmox1 KW - Nqo1 KW - rats U1 - 1997-0838 N2 - Background: The individual effects of psychological stress and food preservatives on the liver—the body’s primary detoxification organ—are well-documented; however, little is known about their combined impact. The aim of this study was to evaluate the hepatic effects of sorbic and benzoic acid exposure in male rats subjected to chronic stress. Results: Over a 28-day period, four groups of male rats were studied: Control, Chronic Stress, Preservatives (sorbic acid at 500 mg/kg and benzoic acid at 100 mg/kg), and a Combined Exposure group. Gene expression analysis revealed increased Sod1 expression under stress conditions, while Nqo1 and Hmox1 were significantly downregulated following preservative exposure and remained suppressed in the combined group. Biochemical analysis demonstrated reduced ALT, AST, and ALP activities across all experimental groups, with the most pronounced decreases observed under combined exposure. LDH activity was elevated under stress but declined when stress was coupled with preservative intake. Lipid metabolism was disrupted, as evidenced by decreased triglyceride levels and altered cholesterol concentrations. Total protein and albumin levels were significantly reduced only in the combined group. Despite preserved hepatic architecture, these molecular and biochemical changes suggest early signs of functional decompensation. Conclusions: Co-exposure to chronic psychological stress and high doses of food preservatives resulted in a non-linear and potentially synergistic disruption of hepatic redox homeostasis, protein synthesis, and lipid metabolism. Further studies incorporating mitochondrial assessment, long-term exposure models, and quantitative interaction analysis are warranted to clarify the mechanisms underlying this toxicological synergy. ER -