Combined photobiomodulation and pulsed electromagnetic field exposure attenuates nitric oxide production in high-glucose/LPS-stimulated RAW264.7 macrophages

PURPOSE: Chronic macrophage inflammation contributes to diabetic complications, highlighting the need for non-pharmacological strategies that regulate inflammatory output without broadly suppressing cellular function. Photobiomodulation (PBM) and pulsed electromagnetic fields (PEMF) can modulate inflammatory and redox-associated responses, but their combined effects under metabolic inflammatory stress remain unclear. This study examined whether concurrent PBM and PEMF regulate the NO/redox-inflammatory axis in high-glucose/LPS-stimulated RAW264.7 macrophages. MATERIALS AND METHODS: ), PEMF (10 Hz pulse repetition frequency, 1.8 mT peak magnetic flux density at the cell plane), or combined PBM and PEMF over a 48-h treatment period. MTT-based metabolic activity, NO-associated nitrite accumulation, TNF-α, IL-6, and IL-1β mRNA expression, and ROS-associated DCFDA fluorescence were evaluated. RESULTS: High glucose and LPS co-stimulation reduced the MTT-based viability signal and increased nitrite accumulation, pro-inflammatory cytokine transcripts, and DCFDA fluorescence. Individual PBM and PEMF treatments preserved the viability signal and attenuated inflammatory markers. Combined PBM and PEMF produced a significant interaction for NO-associated nitrite suppression, reducing nitrite toward the normoglycemic baseline, whereas cytokine transcript attenuation showed no significant interaction. ROS-associated DCFDA fluorescence remained elevated after active treatments, with PEMF contributing strongly to the oxidant-sensitive response. CONCLUSIONS: Concurrent PBM and PEMF selectively attenuated NO-associated inflammatory output while maintaining an active ROS-associated redox state. These findings support a testable dual-input redox-signaling model in which optical and electromagnetic field inputs may converge on macrophage redox signaling. This provides a cautious mechanistic basis for further investigation of combined biophysical stimulation in metabolic inflammation.