The dynamics of reactive oxygen species in photodynamic therapy with tetra sulfophenyl-porphyrin.
Photodynamic therapy (PDT) is a promising therapy especially in skin cancer, using the systemic administration of a photosensitizer (PS), followed by the local irradiation of the tumor with visible light. The antitumor effects of PDT are determined especially by the generation of cytotoxic reactive oxygen species (ROS). The 5,10,15,20-tetra-sulfo-phenyl-porphyrin (TSPP) is a synthetic photosensitizer, which proved its efficiency in in vitro studies. Our study evaluates the effects of PDT with TSPP upon the tumor levels of ROS and upon the metalloproteinases 2 (MMP2) activities on Wistar male rats bearing 256 Walker carcinosarcoma in correlation with the accumulation of PS in the tumor and with the intratumor histological alterations. The evaluations were performed dynamically, at 3 hours, 6 hours, 24 hours and 14 days after the PDT with TSPP. Our results emphasize that 24 hours after the PDT with TSPP, the ROS generation increases, as revealed by protein carbonyls and malondialdehyde levels and the antioxidant capacity (hydrogen donors, thiol groups) decreases in the tumor tissue. These parameters were correlated with the appearance of the histological disorders. The MMP-2 activity increases exponentially in the 24 hours-14 days post PDT interval. PDT with TSPP offers, in vivo , consistent results regarding ROS generation, MMP2 activation and cytotoxic capacity.
Physiology Department, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania. simonaclichici@yahoo.com
Simona
S
Clichici
A
A
Filip
D
D
Daicoviciu
R M
RM
Ion
T
T
Mocan
C
C
Tatomir
L
L
Rogojan
D
D
Olteanu
A
A
Muresan
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002279:Carcinoma 256, Walker / Q000188:drug therapy* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use; D011166:Porphyrins / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors
D000975:Antioxidants; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; C016136:tetraphenylporphine sulfonate; D020778:Matrix Metalloproteinase 2