In vitro phototoxicity of clofibrate. Photochemical and photohemolytic studies on its metabolite clofibric acid.
Aqueous or methanolic solutions of clofibrate and clofibric acid are photolabile towards UVB light under aerobic as well as anaerobic conditions. Nine photoproducts have been identified; their formation involves primary cleavage of the carbon-halogen bond or of the aryloxy-carbon bond, followed by hydrogen abstraction and/or radical recombination. Clofibric acid is phototoxic in vitro as indicated by the photohemolysis test, under both oxygen and argon atmospheres, although the photohemolysis rate is markedly higher under aerobic conditions. Partial inhibition of this process on addition of butylated hydroxyanisole (BHA), reduced glutathione (GSH), sodium azide (NaN3) or 1,4-diazabicyclo[2.2.2]octane (DABCO) suggests the involvement of type I as well as type II mechanisms.
Vargas
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F
Centro de Química, Instituto Venezolano de Investigaciones Científicas IVIC, Caracas.
Canudas
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N
Miranda
M A
MA
Boscá
F
F
D002994:Clofibrate / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D002995:Clofibric Acid / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry; D006461:Hemolysis / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008027:Light; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000633:toxicity*; D013056:Spectrophotometry, Ultraviolet
D017319:Photosensitizing Agents; D002995:Clofibric Acid; D002994:Clofibrate