Photodynamic efficacy of naturally occurring porphyrins in endothelial cells in vitro and microvasculature in vivo.
Photodynamic therapy (PDT) has been described in terms of cellular and vascular effects. The precise mechanisms of cellular and vascular damage are still unknown. In this study, the photodynamic inactivation of endothelial cells in vitro and damage to the microvasculature in vivo by naturally occurring porphyrins (uroporphyrin III (UP), coproporphyrin III (CP) and protoporphyrin IX (PP)) were investigated. The chick chorioallantoic membrane model (CAM model) was used, which is convenient for the study of damage to the microcirculation induced by PDT. The hydrophilic porphyrins UP and CP exhibited low cytotoxicity towards endothelial cells. Only small amounts of UP and CP were taken up, resulting in weak inactivation after irradiation. In contrast, the more lipophilic PP showed a marked cytotoxicity. Considerable amounts of PP were accumulated in the cells, leading to pronounced inactivation after light exposure. For the three porphyrins, damage to the microvasculature was observed. The damage caused by the hydrophilic porphyrins UP and CP was strongly dependent on the drug and light dose. For vascular injury, the efficacy was graded as UP < CP < PP.
Strauss
W S
WS
Institut für Lasertechnologien in der Medizin und Messtechnik an der Universität Ulm, Germany.
Sailer
R
R
Schneckenburger
H
H
Akgün
N
N
Gottfried
V
V
Chetwer
L
L
Kimel
S
S
D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D002645:Chickens; D003306:Coproporphyrins / Q000009:adverse effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D008833:Microcirculation; D010778:Photochemotherapy / Q000009:adverse effects; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000378:metabolism*; D011166:Porphyrins / Q000009:adverse effects / Q000378:metabolism*; D011524:Protoporphyrins / Q000009:adverse effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014578:Uroporphyrins / Q000009:adverse effects / Q000378:metabolism
D003306:Coproporphyrins; D017319:Photosensitizing Agents; D011166:Porphyrins; D011524:Protoporphyrins; D014578:Uroporphyrins; C026971:coproporphyrin III; C022181:uroporphyrin III; C028025:protoporphyrin IX