Flavins are source of visible-light-induced free radical formation in cells

Background and Objectives: It has been hypothesized that reactive oxygen species (ROS) are created by an endogenous photosensitizer during low energy visible light illumination of tissue, and these ROS are responsible for reported biostimulative effects. This study aims to identify the endogenous photosensitizer responsible for ROS production by visible light. Study Design/Materials and Methods: Electron paramagnetic resonance (EPR) spectroscopy was used to detect oxyradicals produced in cardiac and sperm cells during illumination by a halogen lamp. Oxyradical production was determined as a function of illumination wavelength, cell fraction, and molecular weight. Results: Oxyradicals were created solely by the 400-500 nm range of visible light. The endogenous photosensitizer is found predominantly in the cytosol and is smaller than 12 kD. Flavin mononucleotide produces the same signal at concentrations consistent with reported intracellular free flavin concentrations. Conclusions: A small, water soluble photosensitizer active only at wavelengths shorter than 500 nm is consistent with a flavin, which reproduces cellular signals at physiological concentrations. Thus, flavins are responsible for the photosensitization of the observed oxyradicals in cells.