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Y-Y. Huang and others maximized. Therefore the use of LLLT in animals and patients almost exclusively involves red and near-infrared light (600-1100-nm) (Karu and Afanas’eva 1995). The action spectrum (a plot of biological effect against wavelength) shows which specific wavelengths of light are most effective- ly used for biological endpoints as well as for further investigations into cellular mechanisms of phototherapy (Karu and Kolyakov 2005). Fluence (J/cm2) is often referred to as “dose”, though many authors and practi- tioners of LLLT also refer to energy (Joules) as dose. Not only is this con- fusing to the novice student of LLLT but it also assumes that the product of power and time (and more importantly power density and time) is the goal rather than the right combination of individual values. This lack of reciprocity has been shown many times before and since our first paper on biphasic dose response and several more authors have reported find- ing these effects since. Examples of recently published “dose-rate” effects are also reviewed later in this article. Mitochondrial Respiration and Cytochrome c oxidase Mitochondria play an important role in energy generation and metabolism and are involved in current research about the mechanism of LLLT effects. The absorption of monochromatic visible and NIR radia- tion by components of the cellular respiratory chain has been considered as the primary mechanism of LLLT at the cellular level (Karu 1989). Cytochrome c oxidase (Cco) is proposed to be the primary photoaccep- tor for the red-NIR light range in mammalian cells. Absorption spectra obtained for biological responses to light were found to be very similar to the absorption spectra of Cco in different oxidation states (Karu and Kolyakov 2005).LLLT on isolated mitochondria increased proton elec- trochemical potential, ATP synthesis (Passarella et al. 1984), increased RNA and protein synthesis (Greco et al. 1989) and increases in oxygen consumption, mitochondrial membrane potential, and enhanced synthe- sis of NADH and ATP. ROS release and Redox signaling pathway Mitochondria are an important source of reactive oxygen species (ROS) within most mammalian cells. Mitochondrial ROS may act as a modulatable redox signal, reversibly affecting the activity of a range of functions in the mitochondria, cytosol and nucleus. ROS are very small molecules that include oxygen ions such as superoxide, free radicals such as hydroxyl radical, hydrogen peroxide, and organic peroxides. ROS are highly reactive with biological molecules such as proteins, nucleic acids and unsaturated lipids. ROS are also involved in the signaling pathways from mitochondria to nuclei. It is thought that cells have ROS or redox sensors whose function is to detect potentially harmful levels of ROS that 604PDF Image | BIPHASIC DOSE RESPONSE IN LOW LEVEL LIGHT THERAPY AN UPDATE
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