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In Vitro Fluorescence, Toxicity and Phototoxicity Induced by δ‐Aminolevulinic Acid (ALA) or ALA‐Esters
Author(s) -
Eléouet Sabine,
Rousset Nathalie,
Carré Jérôme,
Bourré Ludovic,
Vonarx Véronique,
Lajat Youenn,
Henegouwen Gerard M. J. Beijersbergen,
Patrice Thierry
Publication year - 2000
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2000)0710447ivftap2.0.co2
Subject(s) - phototoxicity , incubation , chemistry , protoporphyrin ix , fluorescence , incubation period , toxicity , hydroxymethyl , in vitro , kinetics , biochemistry , pharmacology , nuclear chemistry , photodynamic therapy , stereochemistry , organic chemistry , biology , physics , quantum mechanics
Synthesis of δ‐aminolevulinic acid (ALA) derivatives is a promising way to improve the therapeutic properties of ALA, particularly cell uptake or homogeneity of protoporphyrin IX (PpIX) synthesis. The fluorescence emission kinetics and phototoxic properties of ALA‐ n ‐pentyl ester (E1) and R , S ‐ALA‐2‐(hydroxymethyl) tetrahydrofuranyl ester (E2) were compared with those of ALA and assessed on C6 glioma cells. ALA (100 μg/mL), E1 and E2 (10 μg/mL) induced similar PpIX‐fluorescence kinetics (maximum between 5 and 7 h incubation), fluorescence being limited to the cytoplasm. The 50% lethal dose occurred after 6 h with 45, 4 and 8 μg/mL of ALA, E1 and E2, respectively. ALA, E1 and E2 induced no dark toxicity when drugs were removed after 5 min of incubation. However, light (25 J/cm 2 ) applied 6 h after 5 min incubation with 168 μg/mL of each compound induced 85% survival with ALA, 27% with E1 and 41% with E2. Increasing the incubation time with ALA, E1 and E2 before washing increased the phototoxicity, but E1 and E2 remained more efficient than ALA, regardless of incubation time. ALA‐esters were more efficient than ALA in inducing phototoxicity after short incubation times, probably through an increase of the amount of PpIX synthesized by C6 cells.