Photodynamic effects induced by meso-tetrakis[4-(carboxymethyleneoxy)phenyl] porphyrin on isolated Sarcoma 180 ascites mitochondria.
Using mitochondria isolated from Sarcoma 180 ascites tumour in Swiss mice as a model system, we have evaluated the ability of a novel porphyrin, meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (H2T4CPP), to induce damage on photosensitization. Oxidative damage to mitochondria, one of the primary and crucial targets of the photodynamic effect, is assessed by measuring products of lipid peroxidation such as thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH), besides the loss of activity of the mitochondrial marker enzyme succinate dehydrogenase (SDH). Analysis of product formation, the effect of deuteration and selective inhibition by scavengers of reactive oxygen species (ROS) show that the damage observed is due mainly to singlet oxygen (1O2) and to a minor extent to hydroxyl radicals (.OH). The 1O2 generation and triplet lifetime of this porphyrin have also been estimated. Fluorescence spectroscopy, used to ascertain the binding of this porphyrin to the mitochondrial proteins, shows a rapid association within 0-2 h and a decline thereafter. Confocal microscopy reveals intracellular localisation of this porphyrin in cells in vitro. Our overall results suggest that the porphyrin H2T4CPP, due to its ability to bind to mitochondrial protein components and to generate ROS upon photoexcitation, may have potential applications in photodynamic therapy.
Chatterjee
S R
SR
Department of Chemistry, Indian Institute of Technology, Powai, Mumbai, India. shampa.chatterjee@medizin.uni-magdeburg.de
Possel
H
H
Srivastava
T S
TS
Kamat
J P
JP
Wolf
G
G
Devasagayam
T P
TP
D000818:Animals; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D008027:Light; D008054:Lipid Peroxides / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000633:toxicity*; D011166:Porphyrins / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012510:Sarcoma 180 / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C105115:tetrakis(4-(carboxymethyleneoxy)phenyl)porphyrin; D013385:Succinate Dehydrogenase