title: Oxidative damage induced by a novel porphyrin on rat brain mitochondria and its possible implications in therapy.
abstract: Free radical-induced oxidative damage is involved in several pathological 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 mitochondria as a model to evaluate the ability of a new water soluble porphyrin, 5,10,15,20-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP), to induce peroxidative damage during photosensitization. Peroxidation in mitochondria, 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 estimated from the loss of a mitochondrial marker enzyme, succinate dehydrogenase (SDH). The photodamage was observed to be time- and concentration-dependent of T4CPP. Inhibition studies suggested involvement of singlet oxygen ((1)O2) and, to a lesser extent, of hydroxyl (OH), peroxyl (ROO(-)) and superoxide radicals (O2(-)) in the photodamage. The addition of γ-linolenic acid (a promoter of lipid peroxidation) to the system led to an enhancement of the T4CPP-induced peroxidative damage. Thus, our study indicated that the combination of γ-linolenic acid and T4CPP could enhance the photodynamic effect and has potential applications in photodynamic therapy.
authors.affiliation: a Department of Chemistry , Indian Institute of Technology , Bombay , India.
authors.forename: S R
authors.initials: SR
authors.lastname: Chatterjee
authors.affiliation: b Cell Biology Division, Bhabha Atomic Research Centre , Bombay , India.
authors.forename: J P
authors.initials: JP
authors.lastname: Kamat
authors.affiliation: a Department of Chemistry , Indian Institute of Technology , Bombay , India.
authors.forename: S J
authors.initials: SJ
authors.lastname: Shetty
authors.affiliation: a Department of Chemistry , Indian Institute of Technology , Bombay , India.
authors.forename: T S
authors.initials: TS
authors.lastname: Srivastava
authors.affiliation: b Cell Biology Division, Bhabha Atomic Research Centre , Bombay , India.
authors.forename: T P
authors.initials: TP
authors.lastname: Devasagayam