OXIDATIVE DAMAGE-INDUCED BY A NOVEL PORPHYRIN ON RAT-BRAIN MITOCHONDRIA AND ITS POSSIBLE IMPLICATIONS IN THERAPY

Free radical-induced oxidative damage is involved in several pathologi cal disorders. On the other hand, selective induction of peroxidation in diseased tissue is a promising approach to the treatment of cancer by photodynamic therapy. In this study we have used rat brain mitochon dria as a model to evaluate the ability of a new water soluble porphyr in, 0-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP), to ind uce peroxidative damage during photosensitization. Peroxidation in mit ochondria, one of the crucial targets of the photodynamic effect, was assessed from the formation of thiobarbituric acid reactive substances and lipid hydroperoxides. The effect on mitochondrial function was es timated from the loss of a mitochondrial marker enzyme, succinate dehy drogenase (SDH). The photodamage was observed to be time-and concentra tion-dependent of T4CPP. Inhibition studies suggested involvement of s inglet oxygen (O-1(2)) and, to a lesser extent, of hydroxyl ((OH)-O-.) , peroxyl (ROO.-) and superoxide radicals (O-2(.-)) in the photodamage . The addition of gamma-linolenic acid (a promoter of lipid peroxidati on) to the system led to an enhancement of the T4CPP-induced peroxidat ive damage. Thus, our study indicated that the combination of gamma-li nolenic acid and T4CPP could enhance the photodynamic effect and has p otential applications in photodynamic therapy.