Destruction of Microsomal Cytochrome P‐450 by Reactive Oxygen Species Generated During Photosensitization of Hematoporphyrin Derivative

Rat liver microsomal cytochrome P‐450 undergoes rapid destruction in the presence of hematoporphyrin derivative (HpD) and solar radiation (∼ 400 nm). Destruction of cytochrome P‐450 is associated with the formation of cytochrome P‐420 and significant loss of microsomal haem. Quenchers of singlet oxygen including 2,5‐dimethylfuran, histidine, ß‐carotene, and ascorbic acid and inhibitors of the hydroxyl radical such as benzoate, mannitol, and ethanol prevent deterioration of the microsomal haem‐protein, whereas superoxide dismutase and catalase are ineffective in this regard. These results indicate that generation of singlet oxygen during hematoporphyrin photosensitization is associated with destruction of microsomal cytochrome P‐450 and haem.