Cellular damage to human hepatocytes through repeated application of 5-aminolevulinic acid

Weiss, Thomas S. and Pahernik, Sascha and Scheruebl, Irmgard and Jauch, Karl-Walter and Thasler, Wolfgang E. (2003) Cellular damage to human hepatocytes through repeated application of 5-aminolevulinic acid. JOURNAL OF HEPATOLOGY, 38 (4). pp. 476-482. ISSN 0168-8278

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Abstract

Background/Aims: 5-Aminolevulinic acid (ALA), a precursor of porphyrins is used for photodynamic diagnosis and therapy within topical or systemic applications. A potential toxic effect on the human liver is of major interest and therefore we investigated the impact of a repeated application of ALA without illumination on cultures of human hepatocytes. Methods: After ALA treatment of hepatocytes in vitro the porphyrin synthesis, albumin secretion, liver-specific enzyme release, and malondialdehyde levels were determined. In order to reduce levels of reactive oxygen substances, mannitol and the antioxidant enzymes superoxide dismutase and catalase were supplemented. Results: Porphyrin biosynthesis by human hepatocytes in vitro was repeatedly stimulated by ALA (0.001-1.0 mM), which was indicated by an accumulation of protoporphyrin IX. A repetitive treatment (up to four times) of hepatocytes with ALA resulted in an impairment of the hepatic function and viability, depending on the ALA concentration (0.1-1.0 mM) and frequency of application (2-3 times). This was also accompanied by increased malondialdehyde levels indicating enhanced lipid peroxidation. Only superoxide dismutase was able to reduce cellular damage and prevent specific function. Conclusions: Repeated, not single, ALA treatment without illumination may cause deleterious effects to the liver, which are mediated by oxygen radicals and inhibited by an antioxidant. (C) 2003 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: DELTA-AMINOLEVULINIC-ACID; LONG-TERM CULTURE; ACUTE INTERMITTENT PORPHYRIA; PHOTODYNAMIC THERAPY; PROTOPORPHYRIN-IX; DNA-DAMAGE; ENDOGENOUS PROTOPORPHYRIN; HYDROGEN-PEROXIDE; HYDROXYL RADICALS; CELLS; 5-aminolevulinic acid; porphyrin; photodynamic therapy/diagnosis; human hepatocyte; reactive oxygen substance; lipid peroxidation; antioxidant
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Medicine > Lehrstuhl für Kinder- und Jugendmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 15 Sep 2021 08:28
Last Modified: 15 Sep 2021 08:28
URI: https://pred.uni-regensburg.de/id/eprint/39158

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