5-aminolevulinic acid (ALA)-induced protoporphyrin IX fluorescence and photodynamic effects in the rat bladder: An in vivo study comparing oral and intravesical ALA administration

Aminolevulinic acid and hexyl-aminolevulinate serve as biological precursors to produce photosensitive porphyrins in cells via the heme biosynthetic pathway. This pathway is integral to porphyrin-based photodynamic diagnosis and therapy. By adding exogenous hexyl-aminolevulinate to rat bladder cancer cells (AY27, in vitro) and an animal bladder cancer model (in vivo), fluorescent endogenous porphyrin production was stimulated. Lipophilic protoporphyrin IX was identified as the dominant species by reverse high-pressure liquid chromatography. Subcellular porphyrin localization in the AY27 cells was evaluated by confocal laser scanning microscopy and showed almost quantitative bleaching after 20 s. From this study, we ascertained that the protocol described herein is suitable for hexyl-aminolevulinate-mediated photodynamic therapy and diagnosis when protoporphyrin IX is the active agent.

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Influence of the menstrual cycle on aminolevulinic acid induced protoporphyrin IX fluorescence in the endometrium: In vivo study

Lasers in Surgery and Medicine ◽

10.1002/lsm.20139 ◽

2005 ◽

Vol 36 (3) ◽

pp. 234-237 ◽

Cited By ~ 3

Author(s):

Andrea Degen ◽

Tanja Gabrecht ◽

Georges Wagnières ◽

Rosmarie Caduff ◽

Bruno Imthurn ◽

...

Keyword(s):

Menstrual Cycle ◽

Aminolevulinic Acid ◽

Protoporphyrin Ix ◽

In Vivo Study

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In Vivo Pharmacokinetics of δ-Aminolevulinic Acid–Induced Protoporphyrin IX During Pre- and Post-Photodynamic Therapy in 7,12-Dimethylbenz(a)nthracene-Treated Skin Carcinogenesis in Swiss Mice: A Comparison by Three-Compartment Model†¶

Photochemistry and Photobiology ◽

10.1562/0031-8655(2002)076<0081:ivpoaa>2.0.co;2 ◽

2002 ◽

Vol 76 (1) ◽

pp. 81 ◽

Cited By ~ 2

Author(s):

Parmeswaran Diagaradjane ◽

Sankaranarayanapillai Madhuri ◽

Prakasarao Aruna ◽

Pradeep Kumar Gupta ◽

Singaravelu Ganesan

Keyword(s):

Photodynamic Therapy ◽

Aminolevulinic Acid ◽

Protoporphyrin Ix ◽

Compartment Model ◽

Skin Carcinogenesis ◽

Swiss Mice ◽

Three Compartment Model ◽

In Vivo Pharmacokinetics

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Chimeric Mouse With Humanized Liver Is an Appropriate Animal Model to Investigate Mode of Action for Porphyria-Mediated Hepatocytotoxicity

Toxicologic Pathology ◽

10.1177/01926233211027474 ◽

2021 ◽

pp. 019262332110274

Author(s):

Ayumi Eguchi ◽

Satoki Fukunaga ◽

Keiko Ogata ◽

Masahiko Kushida ◽

Hiroyuki Asano ◽

...

Keyword(s):

Experimental Model ◽

Mode Of Action ◽

Aminolevulinic Acid ◽

Protoporphyrin Ix ◽

Human Hepatocytes ◽

Chimeric Mouse ◽

Hepatocellular Injury ◽

Hepatocyte Necrosis ◽

Key Events

Porphyrinogenic compounds are known to induce porphyria-mediated hepatocellular injury and subsequent regenerative proliferation in rodents, ultimately leading to hepatocellular tumor induction. However, an appropriate in vivo experimental model to evaluate an effect of porphyrinogenic compounds on human liver has not been fully established. Recently, the chimeric mouse with humanized liver (PXB mice) became widely used as a humanized model in which human hepatocytes are transplanted. In the present study, we examined the utility of PXB mice as an in vivo experimental model to evaluate the key events of the porphyria-mediated cytotoxicity mode of action (MOA) in humans. The treatment of PXB mice with 5-aminolevulinic acid, a representative porphyrinogenic compound, for 28 days caused protoporphyrin IX accumulation, followed by hepatocyte necrosis, increased mitosis, and an increase in replicative DNA synthesis in human hepatocytes, indicative of cellular injury and regenerative proliferation, similar to findings in patients with porphyria or experimental porphyria models and corresponding to the key events of the MOA for porphyria-mediated hepatocellular carcinogenesis. We conclude that the PXB mouse is a useful model to evaluate the key events of the porphyria-mediated cytotoxicity MOA in humans and suggest the utility of PXB mice for clarifying the human relevancy of findings in mice.

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