Padmavathy B, Devaraj H, Devaraj N
Department of Biochemistry, University of Madras, India.
Naunyn Schmiedebergs Arch Pharmacol. 1993 Apr;347(4):421-4. doi: 10.1007/BF00165393.
Amiodarone HCl (AD) is a very effective antiarrhythmic drug, but its use is often associated with serious pulmonary complications. It is shown to induce lung phospholipidosis. Nevertheless, the effects of this drug on pulmonary surfactant which is composed of about 75% phospholipids and which prevents alveolar collapse is not known. Therefore, we have examined the effect of AD on the intra- and extracellular surfactant pools and on the levels of phosphatidylcholine (PC), the primary constituent of pulmonary surfactant. Male Wistar rats were fed AD (175 mg/kg) by oral gavage for three weeks. At the end of the experimental period, the rats were killed, the lungs removed and perfused, and surfactant isolated. Some lungs were prepared for ultrastructural examination. Phospholipid was assayed in the intra- and extracellular surfactant. Amiodarone produced a significant increase in both the intra- and extracellular surfactant phospholipid along with an appreciable change in the phospholipid profile. Also, the drug seemed to increase the number of lamellar inclusions in the surfactant producing type II alveolar cells. These data suggest that administration of AD leads to an increase in the lung surfactant phospholipid levels and lamellar bodies in alveolar type II cells.
盐酸胺碘酮(AD)是一种非常有效的抗心律失常药物,但其使用常伴有严重的肺部并发症。已表明它会诱发肺磷脂沉积症。然而,这种药物对由约75%的磷脂组成且能防止肺泡塌陷的肺表面活性物质的影响尚不清楚。因此,我们研究了AD对细胞内和细胞外表面活性物质池以及对肺表面活性物质的主要成分磷脂酰胆碱(PC)水平的影响。通过口服灌胃给雄性Wistar大鼠喂食AD(175毫克/千克),持续三周。在实验期结束时,处死大鼠,取出肺并进行灌注,然后分离表面活性物质。一些肺被制备用于超微结构检查。对细胞内和细胞外表面活性物质中的磷脂进行了测定。胺碘酮使细胞内和细胞外表面活性物质磷脂均显著增加,同时磷脂谱也有明显变化。此外,该药物似乎增加了产生表面活性物质的II型肺泡细胞中板层小体的数量。这些数据表明,给予AD会导致肺表面活性物质磷脂水平增加以及II型肺泡细胞中的板层小体增多。