Effects of Ketamine and Propofol on Hepatic Oxidative Stress, Inflammatory, and Apoptotic Responses in a Fecal Slurry–Induced Experimental Sepsis Model: The Modulatory Role of Dexmedetomidine

Abstract Background Sepsis is a life-threatening condition characterized by dysregulated host responses, leading to multi-organ dysfunction. The liver plays a central role in metabolic regulation and immune modulation during sepsis and is highly susceptible to oxidative stress, inflammatory injury, and apoptosis. Sedative and anesthetic agents commonly used in septic patients may influence these biological processes beyond their hemodynamic effects; however, their comparative effects on hepatic tissue under septic conditions remain incompletely understood. Methods In this experimental study, polymicrobial sepsis was induced in male Wistar rats using the fecal slurry model. Animals were randomized into six groups: control, sepsis, sepsis + ketamine, sepsis + propofol, sepsis + ketamine + dexmedetomidine, and sepsis + propofol + dexmedetomidine. All drugs were administered intraperitoneally according to predefined dosing protocols. Liver tissues were harvested for biochemical assessment of oxidative stress and inflammatory markers, histopathological evaluation, and immunohistochemical analysis of TNF-α and caspase-3 expression. Results Sepsis was associated with increased oxidative stress, elevated inflammatory markers, and pronounced histopathological liver injury compared with controls. Administration of ketamine or propofol attenuated these alterations, although the effect was limited. In contrast, groups receiving dexmedetomidine in combination with ketamine or propofol demonstrated lower oxidative stress levels, reduced inflammatory and apoptotic marker expression, and milder histopathological damage compared with untreated septic animals. Conclusion In a fecal slurry–induced sepsis model, ketamine and propofol showed partial protective effects on the liver, while the addition of dexmedetomidine was associated with more favorable biochemical, histological, and immunohistochemical findings. These results suggest a potential modulatory role of dexmedetomidine on hepatic injury during experimental sepsis, warranting further investigation in advanced experimental and clinical studies.