Castell J V, Gomez-Lechon M J, Grassa C, Martinez L A, Miranda M A, Tarrega P
Centro de Investigación, Hospital Universitario La Fe (SVS), Valencia, Spain.
Photochem Photobiol. 1993 Mar;57(3):486-90. doi: 10.1111/j.1751-1097.1993.tb02323.x.
Photodegradation of naproxen and tiaprofenic acid in aqueous buffered solutions leads to decarboxylated products with ethyl, 1-hydroxyethyl and/or acetyl side chains. The photomixtures obtained in the presence of oxygen were clearly more toxic to cultured hepatocytes than those obtained under anaerobic conditions. This effect was more noticeable in the case of naproxen. Based on the composition of the oxygenated photomixtures and the relative toxicity of the different photoproducts, it is possible to account for most of the observed toxicity in the case of tiaprofenic acid but not in the case of naproxen. This is explained as a result of the presence of drug-derived peroxidic species in the photomixtures and their contribution to the observed toxicity. Peroxides were determined by the peroxidase-catalyzed oxidation of dichlorodihydrofluorescein to its fluorescent analog. The amount of peroxides present in naproxen photomixtures was much higher than in the case of tiaprofenic acid. A dose-dependent depletion of intracellular glutathione was observed when hepatocytes were incubated with peroxide-containing naproxen photomixtures. This effect was prevented by the addition of catalase or N-acetylcysteine to the culture medium.
萘普生和噻洛芬酸在水性缓冲溶液中的光降解会产生带有乙基、1-羟乙基和/或乙酰基侧链的脱羧产物。在有氧条件下得到的光混合物对培养的肝细胞的毒性明显高于在厌氧条件下得到的光混合物。这种效应在萘普生的情况下更为明显。基于含氧光混合物的组成以及不同光产物的相对毒性，对于噻洛芬酸而言，可以解释所观察到的大部分毒性，但对于萘普生则不然。这可以解释为光混合物中存在药物衍生的过氧化物物种及其对所观察到的毒性的贡献。过氧化物通过过氧化物酶催化二氯二氢荧光素氧化为其荧光类似物来测定。萘普生光混合物中存在的过氧化物量远高于噻洛芬酸的情况。当肝细胞与含过氧化物的萘普生光混合物一起孵育时，观察到细胞内谷胱甘肽呈剂量依赖性消耗。向培养基中添加过氧化氢酶或N-乙酰半胱氨酸可防止这种效应。
