Castell J V, Gomez-Lechon M J, Hernandez D, Martinez L A, Miranda M A
Centro de Investigación, Hospital Universitario La Fe (SVS), Valencia, Spain.
Photochem Photobiol. 1994 Dec;60(6):586-90. doi: 10.1111/j.1751-1097.1994.tb05152.x.
Tiaprofenic acid is a photosensitizing nonsteroidal anti-inflammatory drug, whose major photoproduct (decarboxytiaprofenic acid) is also a potent photosensitizer. Because of the lack of the carboxylate moiety, this photoproduct is more lipophilic and might bind more efficiently to cell membranes, thereby causing phototoxic damage. To verify the feasibility of this hypothesis, we have prepared the 3H-labeled analogs of tiaprofenic acid and its photoproduct and examined the binding, persistence and phototoxicity of the photoproduct using poorly metabolizing (fibroblasts) and actively metabolizing cells (hepatocytes). The photoproduct of tiaprofenic acid accumulates in both cell types as it is formed. Upon removal of the photoproduct from the culture medium, it rapidly disappears from hepatocytes but not from fibroblasts. Consequently, irradiation of fibroblasts previously incubated with the photoproduct and kept in culture in the dark for 20 h results in generalized cell damage while this effect is not observed in hepatocytes. Because of its long persistence in poorly metabolizing skin cells and its reluctance to photobleaching, the formation of this photoproduct in skin may be of relevance to explain the in vivo phototoxicity of tiaprofenic acid.
噻洛芬酸是一种具有光敏性的非甾体抗炎药，其主要光产物（脱羧噻洛芬酸）也是一种强效光敏剂。由于缺乏羧基部分，这种光产物具有更强的亲脂性，可能更有效地与细胞膜结合，从而导致光毒性损伤。为了验证这一假设的可行性，我们制备了噻洛芬酸及其光产物的3H标记类似物，并使用代谢缓慢的细胞（成纤维细胞）和代谢活跃的细胞（肝细胞）研究了光产物的结合、持久性和光毒性。噻洛芬酸的光产物在形成后会在两种细胞类型中积累。从培养基中去除光产物后，它会迅速从肝细胞中消失，但不会从成纤维细胞中消失。因此，对预先用该光产物孵育并在黑暗中培养20小时的成纤维细胞进行照射会导致细胞普遍受损，而在肝细胞中未观察到这种效应。由于其在代谢缓慢的皮肤细胞中持续存在时间长且不易发生光漂白，皮肤中这种光产物的形成可能与解释噻洛芬酸在体内的光毒性有关。
