title: Malondialdehyde dosimetry in laser-irradiated tissues sensitized by hematoporphyrin derivative.
abstract: Photodynamic therapy (PDT) is based on the selective retention of a photosensitizer (hematoporphyrin derivative [HPD]) by tumor tissue and the subsequent irradiation of this tissue with light. Unsaturated phospholipids are important targets of membrane photodamage, and malondialdehyde (MDA), an ultimate marker of lipid peroxidation, can easily be measured by the fluorometric thiobarbituric acid (TBA) assay. To determine whether MDA content represents a reference for PDT intensity, tissue content in 7-week-old male nude mice was studied on biopsy samples after PDT (5 mg/kg HPD injected intravenously 24 hr before irradiation at 632 nm) with or without intraperitoneal injection of WR-2721 40 min before treatment. The FeCl3 method requiring only 15 min of incubation in a 95 degrees C waterbath proved most effective compared with the method involving phosphotungstic acid or the MDA-TBA determination using a commercially available kit. Whatever the method used, the best results were found using a 60-min interval between treatment and freezing. MDA concentration in HPD-PDT-treated samples was significantly higher than in HPD-tested controls (P < .01) and increased at laser irradiation doses ranging from 0 to 50 J/cm2. Administration of WR-2721 intraperitoneally significantly reduced MDA concentration (from 70% to 38%). A maximal effect was obtained with 100 mg/kg for brain (-70%) and 200 mg/kg for muscle (-47%). Higher doses produced no additional changes. The MDA assay is a simple tool for indirect evaluation of PDT, and WR-2721 can decrease MDA content in normal tissue, suggesting the possibility of good protection for normal tissue during PDT.
authors.affiliation: Faculté de Pharmacie, Nantes Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Perret
authors.forename: M T
authors.initials: MT
authors.lastname: Foultier
authors.forename: V
authors.initials: V
authors.lastname: Vonarx-Coinsman
authors.forename: O
authors.initials: O
authors.lastname: Quancard
authors.forename: A
authors.initials: A
authors.lastname: Combre
authors.forename: T
authors.initials: T
authors.lastname: Patrice
mesh_terms: D004999:Amifostine / Q000494:pharmacology; D000818:Animals; D017324:Hematoporphyrin Derivative / Q000494:pharmacology*; D007834:Lasers; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D011833:Radiation Injuries, Experimental / Q000378:metabolism*; D015203:Reproducibility of Results; D013858:Thiobarbiturates / Q000378:metabolism
chemical_list: D013858:Thiobarbiturates; D008315:Malondialdehyde; D017324:Hematoporphyrin Derivative; C029684:thiobarbituric acid; D004999:Amifostine