Abstract
It was investigated whether drug-induced phospholipidosis was caused by thymoxamine hydrochloride, [2- (4-acetoxy-2-isopropyl-5-methylphenoxy) -N, N-dimethylamine hydrochloride] (thymoxamine) in rat, compared with chloroquine diphosphate (chloroquine) . In vitro studies, the lysosomal phospholipase C activities were inhibited markedly by chloroquine but were unaffected by thymoxamine. In vivo studies, rats were administered intraperitoneally with thymoxamine (15 mg/kg, 30 mg/kg) or chloroquine (15 mg/kg, 30 mg/kg and 60 mg/kg) for two weeks. Thymoxamine did not inhibit the lysosomal phosholipase -A and -C activities of rat's liver. Administration of chloroquine to rat caused a tendency to inhibit the lysosomal phospholipase C activities. No significant changes were noted in values of the blood, liver and liver-lysosomal biochemical parameters or pathological examinations treated with thymoxamine. On the othe hand, chloroquine caused remarkably total-cholesterol, triglyceride and phospholipids accumulation in lysosomal fraction of rats, and was also showed marked rise of s-GOT and m-GOT. Because chloroquine inhibited directly or indirectly the lysosomal phospholipase, in paticular phospholipase C, and caused characteristic drug-induced phospholi-pidosis. In comparison with chloroquine, there were no results to prove that phospholipidosis was induced by thymoxamine.
