Effect of chloroquine wash-out period of photosensitizers in the skin and selected organs in rats.
In the last decade, photodynamic therapy has become an alternative method for the diagnosis and therapy of tumors. In human medicine hematoporphyrin derivatives, sulfonated hydrophilic meso-tetraphenylporphyrin (TPPS4) and an oligomer of hematoporphyrin (Photosan 3), are widely used. Chloroquine is used for the treatment of porphyria cutanea tarda for its power to release porphyrins from the liver tissue. The kinetics of two porphyrin photosensitizers TPPS4 and Photosan 3 in the skin and some organs as well as the effect of chloroquine on the porphyrin excretion and their accumulation in skin and organs of Wistar rats were studied. TPPS4 exhibited maximum fluorescence in skin 48 h after application with decreasing to basal level from the 8th to the 14th day. Maximum fluorescence was reached at 72 hours after Photosan 3 application and it decreased to basal level during 96 hours after application. TPPS4 caused significantly higher fluorescence compared to Photosan 3. Chloroquine after oral administration did not change the fluorescence of skin, but it significantly decreased the TPPS4 concentration in rat organs if chloroquine treatment started 3 days or 2 weeks after TPPS4 application. Chloroquine significantly decreased the serum TPPS4 concentration during the period of 28 days. Fluorescence of skin was significantly higher and lasted longer after application of TPPS4 compared to Photosan 3. Chloroquine after oral administration did not influence the fluorescence of the skin, but it significantly decreased the TPPS4 concentration in rat organs. This effect could be useful in photodynamic therapy for mobilizing exogenous porphyrins from tissues after parenteral photodynamic therapy.
Institute of Clinical Chemistry, First Faculty of Medicine, Charles University, Prague 2, Czech Republic. zimatom@cesnet.cz
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Zima
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Jirsa
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Jirsa
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Jirásková
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Bradová
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Stádník
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005453:Fluorescence; D006415:Hematoporphyrins; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000097:blood / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D000962:Antimalarials; D006415:Hematoporphyrins; D017319:Photosensitizing Agents; D011166:Porphyrins; C071875:photosan III; C016136:tetraphenylporphine sulfonate; D002738:Chloroquine