Lipid peroxidation induced by meso-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]prophyrin on photosensitization in hepatic and tumor microsomes

The ability of a novel porphyrin, meso-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]porphyrin (T3,4-CPP), to induce photodamage in subcellular membranes, in the form of rat hepatic and tumor microsomes, was evaluated with a view to locating suitable porphyrin derivative for possible use in photodynamic therapy. This water-soluble porphyrin, on exposure to visible light, induced a significant extent of membrane lipid peroxidation as assessed by the formation of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes. The peroxidation induced in hepatic microsomes is both time-and concentration-dependent. Using inhibitors of reactive oxygen species and comparing products of peroxidation, it is shown that the damage induced is mainly due to singlet oxygen and partly due to other species like free radicals. T3,4-CPP also caused the generation of singlet oxygen as a function of illumination time. Since membrane damage induced by a sensitizer on photoexcitation has been considered to be an important mechanism by which photodynamic cell killing of tumor occurs, the studies on this novel porphyrin indicate the possible potential of this compound in photodynamic therapy. (C) 1997 Elsevier Science Ireland Ltd