Photohaemolysis assay for drug phototoxicity complicated by 'bleaching' of released haemoglobin

Toxicology in Vitro : an International Journal Published in Association with BIBRA
N J TraynorN K Gibbs

Abstract

The phototoxic potential of several non-steroidal anti-inflammatory drugs and quinolone antibiotics was assessed using the photohaemolysis assay. In this system, human erythrocytes are irradiated (UVA radiation 320-400 nm) from below in the presence of suspected photosensitizers. Photohaemolysis with ketoprofen, tiaprofenic acid or nalidixic acid was initially concentration dependent, but photohaemolysis apparently decreased at higher drug concentrations. As erythrocytes were irradiated from below any optical screening at high drug concentrations was discounted. Other phototoxic drugs can oxidize haemoglobin to methaemoglobin resulting in a decrease in absorption and an artificially lowered photohaemolysis level. However, in the present experiments, the use of Drabkin's solution overcame this effect as haemoglobin and most of its oxidized derivatives were converted into a single derivative, namely cyanmethaemoglobin. Further possibilities are that photosensitized damage to haemoglobin results in the formation of intracellular Heinz bodies and/or bleaching of released haemoglobin. The latter hypothesis was tested by irradiating free haemoglobin in the presence of drugs. The results suggested that certain phototoxic agents cause ...Continue Reading

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Citations

Jul 17, 2010·Journal of Photochemistry and Photobiology. B, Biology·H R VardapetyanA A Hovhannisyan
Aug 5, 2005·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Yuko Okamoto
Jul 1, 1999·Alternatives to Laboratory Animals : ATLA·Y OkamotoK Ohkoshi
Oct 1, 2005·Alternatives to Laboratory Animals : ATLA·Manfred LiebschChantra Eskes
Dec 6, 2000·Alternatives to Laboratory Animals : ATLA·H SpielmannUNKNOWN European Centre for Validation of Alternative Methods
Dec 1, 2004·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Lars KaestnerJohan Moan
Feb 24, 2007·The Journal of Physical Chemistry. B·Hiroyuki SuzukiMichinori Sakai

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