Abstract
Photodynamic therapy is selective destruction of cells stained with a photosensitizer upon irradiation with light at a specific wavelength in the presence of oxygen. Cell death upon photodynamic treatment is known to occur mainly due to free radical production and subsequent development of oxidative stress. During photodynamic therapy of brain tumors, healthy cells are also damaged; considering this, it is important to investigate the effect of the treatment on normal neurons and glia. We employed live-cell imaging technique to investigate the cellular mechanism of photodynamic action of radachlorin (200 nM) on neurons and astrocytes in primary rat cell culture. We found that the photodynamic effect of radachlorin increases production of reactive oxygen species measured by dihydroethidium and significantly decrease mitochondrial membrane potential. Mitochondrial depolarization was independent of opening of mitochondrial permeability transition pore and was insensitive to blocker of this pore cyclosporine A. However, irradiation of cells with radachlorin dramatically decreased NADH autofluorescence and also reduced mitochondrial NADH pool suggesting inhibition of mitochondrial respiration by limitation of substrate. This effect could be prevented by inhibition of poly (ADP-ribose) polymerase (PARP) with DPQ. Thus, irradiation of neurons and astrocytes in the presence of radachlorin leads to activation of PARP and decrease in NADH that leads to mitochondrial dysfunction.
Highlights
Photodynamic therapy is selective destruction of cells stained with a photosensitizing agent upon irradiation with light at a specific wavelength in the presence of oxygen [1, 2]
We have found that illumination of cells with the radachlorin leads to mitochondrial depolarization in both neurons and astrocytes and decrease of mitochondrial NADH level
We show that PDT with radachlorin alters mitochondrial metabolism in neurons and astrocytes that can be a possible mechanism for cell death as for targeted cells as well as for surrounding healthy cells
Summary
Photodynamic therapy is selective destruction of cells stained with a photosensitizing agent (photosensitizer) upon irradiation with light at a specific wavelength in the presence of oxygen [1, 2]. It is applied in oncology for treatment of different tumors, including brain tumors [3, 4]. Cell death upon photodynamic treatment is known to occur mainly due to production of reactive oxygen species (ROS) by the photosensitizer [1]. The exact mechanisms of the cell death could vary for different photosensitizing agents depending on the places of their accumulation, their ability to produce ROS, etc. During photodynamic therapy of brain tumors, healthy cells are damaged; considering this, unraveling the effects of irradiation of photosensitizers on normal neurons and glial cells is important for prevention of possible side effects during the treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
