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PHOTOPRODUCTS OF CHLORPROMAZINE WHICH CAUSE RED BLOOD CELL LYSIS
Author(s) -
Kochevar Irene E.,
Hom Jennie
Publication year - 1983
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1983.tb04452.x
Subject(s) - chemistry , phototoxicity , lysis , chlorpromazine , sephadex , membrane , fluorescence , dimethyl sulfoxide , band 3 , absorption band , mole , chromatography , photochemistry , nuclear chemistry , biochemistry , membrane protein , organic chemistry , in vitro , enzyme , biology , physics , quantum mechanics , optics , endocrinology
A mechanism for chlorpromazine (CPZ) phototoxicity has been proposed that attributes the response to formation of stable, toxic photoproducts which cause cell membrane disruption. We have characterized these toxic photoproducts as dimers and higher multimers of CPZ. Chlorpromazine solutions (3 or 10 mA/) were irradiated with a medium pressure Hg lamp filtered to exclude λ < 280 nm. Five low mol wt photoproducts were separated by high performance liquid chromatography. Two were identified as CPZ‐sulfoxide and promazine. Higher mol wt photoproducts were separated by Sephadex G‐50 chromatography into 3 broad bands which were characterized by their absorption and fluorescence spectra. Band A (mol wt > 800) had λ max abs = 263 nm, λ max fl = 490 nm and Band B (mol wt = 350‐800) had λ max abs = 255 nm, λ max fl = 450 nm. Based on the mol wt of CPZ, Band A contained trimers and higher mol wt compounds and Band B was composed of dimeric structures. BandC(λ max abs = 255,310 nm; λ max fl = 445 nm) was composed of CPZ (mol wt = 315) and the low mol wt photoproducts. Red blood cell lysis was used as an assay for the ability of photoproducts to cause membrane disruption. Bands A and B, but not Band C, caused cell lysis. These data indicate that the CPZ photoproducts which cause cell membrane disruption are dimers (Band B) and higher multimers (Band A).