title: Photodynamic effects of chloroaluminum phthalocyanine tetrasulfonate are mediated by singlet oxygen: in vivo and in vitro studies utilizing hepatic microsomes as a model membrane source.
abstract: Chloroaluminum phthalocyanine tetrasulfonate (AlPcTS) is a promising photosensitizer for the photodynamic therapy (PDT) of cancer. In this study, we investigated the in vivo and in vitro photodestruction of hepatic microsomal membranes by AlPcTS and studied the role of reactive oxygen species in this process. Irradiation of hepatic microsomes prepared from AlPcTS-pretreated SENCAR mice to approximately 675 nm light resulted in rapid destruction of cytochrome P450 and associated monooxygenase activities, and enhancement of lipid peroxidation in a light-dose-dependent manner. The specificity of AlPcTS and light dependency on photodestruction of microsomal membranes was confirmed by Western blot analysis. Similar results were obtained when AlPcTS was added in vitro to a suspension of hepatic microsomes prepared from control animals followed by irradiation to approximately 675 nm light. Among the quenchers of singlet oxygen, superoxide anion, hydrogen peroxide, and hydroxyl radical, only the quenchers of singlet oxygen such as sodium azide, histidine, and 2,5-dimethyl furan afforded substantial protection in a dose-dependent manner against AlPcTS-mediated photodestruction of cytochrome P450 and associated monooxygenase activities, and photoenhancement of lipid peroxidation under both in vivo and in vitro conditions. These results suggest that lipid-rich microsomal membranes may be the potential targets of cell injury by AlPcTS-based PDT and that this process is mediated by singlet oxygen.
authors.affiliation: Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, Ohio.
authors.forename: R
authors.initials: R
authors.lastname: Agarwal
authors.forename: S I
authors.initials: SI
authors.lastname: Zaidi
authors.forename: M
authors.initials: M
authors.lastname: Athar
authors.forename: D R
authors.initials: DR
authors.lastname: Bickers
authors.forename: H
authors.initials: H
authors.lastname: Mukhtar
mesh_terms: D000818:Animals; D001386:Azides / Q000494:pharmacology; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D005663:Furans / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects; D008027:Light; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D026082:Singlet Oxygen; D019810:Sodium Azide
chemical_list: D001386:Azides; D005663:Furans; D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C052736:chloroaluminum tetrasulfophthalocyanine; D026082:Singlet Oxygen; D006639:Histidine; D003577:Cytochrome P-450 Enzyme System; D019810:Sodium Azide; C037555:2,5-dimethylfuran; D010100:Oxygen