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J Hepatol. 2003 Apr;38(4):476-82.

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

Author information

1
Center for Liver Cell Research, University of Regensburg Hospital, F.-J.-S.-Allee 11, D-93042 Regensburg, Germany. thomas.weiss@klinik.uni-regensburg.de

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.

PMID:
12663240
DOI:
10.1016/s0168-8278(02)00454-3
[Indexed for MEDLINE]

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