Norwegian Radiation Protection Authority

Introduction

Metalloporphyrins have been shown to inhibit heme oxygenase (HO) and thus to suppress the formation of bilirubin in humans as well as in experimental animals. This may be taken advantage of in the treatment of hyperbilirubinemia in newborns (1).

Phototherapy is the standard therapy of moderate hyperbilirubinemia. Since porphyrins are known photosensitisers (2), there is a possibility that they may induce adverse phototoxic effects. Photosensitising effects of tin-protoporphyrin (SnPP), probably introduced by the formation of singlet oxygen, has been observed both in vitro and in vivo (1,3). The photosensitising effects of different metalloporphyrins may differ from each other depending on physiochemical and other properties (4,5). Among the different metalloporphyrins tested by Vreman et al. (4) several compounds were found to exhibit photosensitising effects on bilirubin, NADH or whole animals, while neither Cr-mesoporphyrin (CrMP) nor Cr-protoporphyrin (CrPP) showed any significant photosensitising effect. Both Cr-derivatives inhibit HO efficiently.

It has been shown previously that visible light can lead to the formation of DNA-damage in cultured cells (6), and that bilirubin under certain in vitro conditions will lead to photosensitised DNA-damage and cytotoxic effects on cells (7,8,9,10).

This study will focus on the photodynamic effects of metalloporphyrins. Do photoreactions in the presence of metalloporphyrins cause cytotoxicity or DNA-damage as has been shown for other porphyrins (11,12)? Will bilirubin suppress the photosensitising effect of the porphyrins due to its known anti-oxidant properties (13,14,15)?

Particularly the interaction with DNA and cytotoxic effects is of interest since other porphyrins are well known photodynamic agents (11,12). If the metalloporhyrins show different photodynamic activities, the differences may be a factor that should be taken into consideration when evaluating them as chemotherapeutic agents. This is particularly important if the use of metalloporhyrin-therapy is going to be used in combination with phototherapy. Bilirubin is an antioxidant (13,14,15) and the presence of high concentrations of bilirubin may reduce the effects of metalloporhyrins and light. The cellular effects of photosensitisation by metalloporhyrins combined with bilirubin will be presented.

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