Electromagnetic Biology and Medicine, 2025 (SCI-Expanded)
The aim of this study is to investigate the potential synergistic effects of agomelatine(AGM) and 2600 MHz radiofrequency(RF) field exposure on inflammation induced by chronic lipopolysaccharide(LPS) administration in rats. A total of 49 female Wistar albino rats were randomly divided into 7 groups(n = 7 per group): Control, Sham, LPS, LPS+AGM,LPS+RF,AGM+RF, and LPS+AGM+RF. Animals in the RF groups were exposed to a 2600 MHz field (1 h/day for 15 days). The whole-body averaged SAR was calculated to be 0.637 W/kg, while the localized SAR values were found to be 1.27 W/kg for 1 g and 0.91 W/kg for 10 g of brain tissue at a frequency of 2600 MHz. Chronic LPS administration(1 mg/kg/day for 15 days) successfully induced a systemic inflammatory state. The most significant finding was observed in plasma IL-6 levels. While AGM or RF exposure alone did not significantly alter IL-6 levels in LPS-treated animals, the combined treatment of LPS+AGM+RF resulted in a substantial and statistically significant decrease in plasma IL-6 compared to the sham group(p < 0.001). This represents a large-magnitude effect (Cohen’s d = 1.59), suggesting a potent anti-inflammatory action of the combined therapy. In contrast, plasma IL-1β and TNF-α levels showed no statistically significant differences among any of the groups. In the hypothalamus, chronic LPS exposure was associated with a downregulation of MAP kinase signaling pathways (ERK, JNK), indicative of endotoxin tolerance, and with reduced NF-κB level. This study provides novel evidence that 2600 MHz RF, when combined with AGM, may exert a powerful anti-inflammatory effect, highlighting a potential therapeutic interaction that warrants further investigation.