The cytotoxic activity of hematoporphyrin: studies on the possible role of transition metals.
Hematoporphyrin acquires a potent cytolytic activity toward erythrocytes when activated by visible light. Considerable evidence has been obtained suggesting that this toxic activity is mediated by certain active oxygen species, including singlet oxygen and hydroxyl radicals. These active oxygen species have also been proposed as intermediates in the toxic activity of peroxidases, hemin, and a variety of metal complexes. Unlike hematoporphyrin, all these compounds contain a liganded Fe atom, which appears to play a central role in the activation of molecular oxygen. In order to ascertain whether the generation of active oxygen by hematoporphyrin may also involve the participation of a metal ion we have compared the cytolytic activity of hematoporphyrin with that of hematoheme. The participation of a metal ion in the light-activated hematoporphyrin reaction was ruled out on the basis of four criteria: no increase in cytolytic activity was observed upon the addition of Fe or Cu ions; no evidence could be obtained for the incorporation of a metal ion into hematoporphyrin during light activation; hematoporphyrin is a more potent cytolytic agent than hematoheme on an equimolar basis; and the activities of the two cytolytic agents are affected differently by various activators and inhibitors of the toxic reaction. Our results further indicate that the mechanism of the cytolytic activity promoted by light-activated hematoporphyrin is distinctly different from that promoted by hematoheme in the presence of ascorbate. We conclude that the two cytolytic reactions are most likely propagated by two different forms of active oxygen.
D000818:Animals; D003300:Copper / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects*; D006415:Hematoporphyrins / Q000528:radiation effects / Q000633:toxicity*; D006427:Hemin / Q000633:toxicity; D007501:Iron / Q000494:pharmacology*; D008027:Light; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits
D006415:Hematoporphyrins; D011725:Pyridines; D006427:Hemin; D003300:Copper; D007501:Iron