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Evaluation expérimentale de la Protoporphyrine IX (PpIX) induite par l'hexylester d'acide 5-aminolévulinique (hALA), et de l'hypéricine pour le traitement photodynamique de tumeurs de vessie

Abstract : Biosynthesis and photodynamic eflicacy of protoporphyrin IX (PpIX) generated by 5-aminolevulinic acid hexylester (hALA) were studied in vitro using AY27 cells and in vivo on healthy or tumor-bearing rats. The orthotopic bladder tumors were induced with AY27 cells in Fischer rats. ln vitro, the total PpIX content at the end of 2 h incubation was at least 1.5-fold greater with hALAcompared to 5-aminolevulinic acid (ALA) despite the dlfference in concentratibn of several orders between the two compounds (1 or 5 mM ALA and 5 or 10 x 10- 3 mM hALA). ln vivo, the maximal tumor : healthy tissue ratio of 5:1, determined by laser induced fluorescence (LIF), was reached 3 and 4 h after instillation of 3 and 12 mM hALA respectively. The photodynamic therapy (PDT) at this time conduced to different grades of tumor tissue damage, including complete tumor eradication. ln healihy tissue, there was a high inflammatory reaction without neerosis in the muscle layers. The photodynamic effects were observed 24 h after irradiation at 635 nm. Globally the in vitro and in vivo effects were not modified by the hALA concentration increase from 5 x 10-3 to 10 X 10-3 mM and from 3 to 12 mM respectively. Hypericin biodistribution and efflux in an orthotopic rat bladder tumor model were also investigated using fluorescence microscopy and LIF techniques. Hypericin (8 or 30/lM) was instilled for 1, 2 or 4 h into the bladder of healthy and tumor-bearing rats. The results showed higher hypericin fluorescence in the tumor than in the normal bladder, with the tumor to normal bladder ratio reaehing 12:1 afler 4 h of hypericin (30 uM) instillation. Moreover, hypericin was retained in the tumor for at least 1 h before a gradual lost from the tissue. Microscopically, the fluorescence of hypericin was restricted to the tumor and to the normal urothelium without fluorescence in the submucosa and the muscle layers. Subsequently no hypericin was detected in plasma, indicating that under these conditions systemic side effects should not be expected.
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http://docnum.univ-lorraine.fr/prive/SCD_T_2001_0272_COSSERAT_GERARDIN.pdf
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https://hal.univ-lorraine.fr/tel-01746483
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Submitted on : Thursday, March 29, 2018 - 10:38:47 AM
Last modification on : Friday, October 23, 2020 - 10:33:45 AM

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Isabelle Cosserat-Gerardin. Evaluation expérimentale de la Protoporphyrine IX (PpIX) induite par l'hexylester d'acide 5-aminolévulinique (hALA), et de l'hypéricine pour le traitement photodynamique de tumeurs de vessie. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2001. Français. ⟨NNT : 2001NAN11308⟩. ⟨tel-01746483⟩

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