Bispinck F, Fischer J, Lüllmann-Rauch R, Ziegenhagen M W
Department of Pharmacology, University of Kiel, Germany.
Exp Toxicol Pathol. 1998 Sep;50(4-6):411-5. doi: 10.1016/S0940-2993(98)80027-4.
Dicationic amphiphilic drugs such as the immunomodulator tilorone [2,7-bis-[2-(diethylamino)ethoxy]fluoren-9-one] are accumulated in lysosomes and disturb the degradation of sulphated glycosaminoglycans (GAGs) thus leading to generalized lysosomal GAG storage (mainly dermatan sulphate) in vivo and in cultured cells. In the present study, the time course of the tilorone-induced GAG storage was determined in cultured bovine corneal fibroblasts by a radiochemical approach and by morphological examination. In contrast to the rapid lysosomal accumulation of the drug as reported previously, it took approximately 42 h to reach 50% of the GAG storage obtained after 96 h. This is thought to be due to the fact that the temporal development of storage of undigested GAGs depends on the natural delivery of GAGs towards the lysosomal apparatus.
双阳离子两亲性药物，如免疫调节剂替洛隆[2,7-双-[2-(二乙氨基)乙氧基]芴-9-酮]，会在溶酶体中蓄积，并干扰硫酸化糖胺聚糖（GAGs）的降解，从而在体内和培养细胞中导致全身性溶酶体GAG蓄积（主要是硫酸皮肤素）。在本研究中，通过放射化学方法和形态学检查，确定了替洛隆诱导的GAG蓄积在培养的牛角膜成纤维细胞中的时间进程。与之前报道的药物迅速在溶酶体中蓄积不同，达到96小时后获得的GAG蓄积量的50%大约需要42小时。这被认为是由于未消化的GAG蓄积的时间发展取决于GAG向溶酶体装置的自然输送。
