Synergistic mitigation of endotoxin-induced liver injury by low-frequency PMF and 27.12 MHz RF-EMF: a multi-biomarker experimental study.

BACKGROUND: Sepsis-associated liver injury is a major cause of morbidity and mortality, with oxidative stress, inflammation, and apoptotic signaling playing central roles in pathogenesis. Non-invasive physical modalities such as pulsed magnetic fields (PMF) and radiofrequency electromagnetic fields (RF-EMF) have shown organ-protective effects in various experimental settings; however, their combined application in hepatic inflammation has not been previously investigated. METHODS: Forty female Wistar rats were randomized into five groups: Control, LPS, LPS + PMF, LPS + RF, and LPS + PMF+RF. Acute liver injury was induced with intraperitoneal LPS. PMF and RF-EMF were applied individually or in combination. Liver tissues were analyzed by histopathology, immunohistochemistry, and RT-qPCR for oxidative (NRF2, SOD), inflammatory (TNF-α), mitochondrial apoptotic (BCL2, BAX, Cyt-C, Caspase-9), and ER stress (PERK, Caspase-12, Caspase-3) markers. Serum ALT, AST, and albumin levels were also measured. RESULTS: LPS significantly increased TNF-α, BAX, Cyt-C, Caspase-9, PERK, Caspase-12, and Caspase-3 expression, while decreasing NRF2, SOD, and BCL2 (all ***p < 0.001). Both PMF and RF monotherapies partially restored these parameters; however, the combined PMF + RF application achieved the most pronounced effects at the molecular and histopathological levels, normalizing oxidative stress markers, reducing pro-inflammatory and apoptotic signaling, and improving histopathological scores (all **p < 0.05 to ***p < 0.001 vs. LPS). Serum AST and ALT levels were significantly reduced by PMF monotherapy, while RF and combined PMF + RF treatments also produced significant decreases compared to the LPS group, albeit to a lesser extent. Serum albumin levels remained unchanged across all groups. CONCLUSION: Concurrent low-frequency PMF and RF-EMF exposure confers synergistic hepatoprotection in endotoxin-induced liver injury by modulating oxidative, inflammatory, and apoptotic pathways. These findings suggest that dual-modality PMF and RF-EMF exposure may represent a promising non-invasive experimental strategy for mitigating endotoxin-driven hepatic injury. Further studies in clinically relevant sepsis and ischemia-reperfusion models, with extended follow-up and mechanistic validation, are warranted before translational inference. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00068-026-03119-2.