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Photoenhancement of Lipid Peroxidation Associated with the Generation of Reactive Oxygen Species in Hepatic Microsomes of Hematoporphyrin Derivative-treated Rats¹

Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, and Veterans Administration Medical Center, Cleveland, Ohio 44106

Hepatic microsomes prepared from rats pretreated with hematoporphyrin derivative (HPD) undergo rapid enhancement of lipid peroxidation in the presence of solar radiation (400 nm). Quenchers of singlet oxygen, including 2,5-dimethylfuran, histidine, and ß-carotene, and inhibitors of the hydroxyl radical, including benzoate, mannitol, and ethanol, largely protected against the enhancement of lipid peroxidation caused by HPD photosensitization. Catalase, a scavenger of hydrogen peroxide and superoxide dismutase, a scavenger of superoxide anion, had little or no protective effect against HPD-photosensitized enhancement of lipid peroxidation. Our data indicate that in vitro irradiation of hepatic microsomes prepared from HPD-treated rats results in the generation of both singlet oxygen and hydroxyl radical. These reactive moities are associated with a rapid increase in microsomal lipid peroxidation which may explain the unique susceptibility of membranous components of cells to this type of phototoxic injury.

¹ Supported by NIH Grants CA 34368, ES-1900, and CA-38028 and by research funds from the Veterans Administration.

² Recipient of the Burroughs Wellcome Fund fellowship award from the Dermatology Foundation. To whom requests for reprints should be addressed, at Veterans Administration Medical Center, 10701 East Boulevard, Cleveland, OH 44106.

Received 1/ 8/85. Revised 8/23/85. Accepted 9/ 9/85.