Cellular damage to human hepatocytes through repeated application of 5-aminolevulinic acid.
OBJECTIVE
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.
Weiss
Thomas S
TS
Center for Liver Cell Research, University of Regensburg Hospital, F.-J.-S.-Allee 11, D-93042 Regensburg, Germany. thomas.weiss@klinik.uni-regensburg.de
Pahernik
Sascha
S
Scheruebl
Irmgard
I
Jauch
Karl-Walter
KW
Thasler
Wolfgang E
WE
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology
D000975:Antioxidants; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; D000622:Aminolevulinic Acid; D013482:Superoxide Dismutase