The term photobiomodulation (PBM), where modulation usually implies a positive or negative response, has been used to describe a photostimulation effect on cells and tissues that leads to beneficial physiological outcomes, such as increased cellular energetics (ATP) and faster healing. Literature points to multiple hypotheses for the mechanism of PBM therapy when using light in the wavelength range of red to near infrared (NIR). We have used a variety of methods and experimental systems to measure light-dependent biological effects in response to laser parameters that would be expected to produce the physiological effects associated with PBM. Here, we highlight two in vitro experiments addressing two different hypotheses for the mechanism of PBM initiation. First, based on wavelength-dependent efficiencies for nitric oxide (NO) release in hTERT-RPE1 cells, we have used these dependences to determine if optimal NO release correlates to increased activity of complex C-IV in the electron transport chain (ETC). Second, to find any indication that water vibration can lead to stimulation of C-IV activity, we exposed isolated mitochondria with laser light at a frequency of 2.52 terahertz (THz) and compared the results with photostimulation of C-IV activity at 808 nm.
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