Ford D M, Thieme R E, Lamp C A, Covington S J, Molitoris B A
Department of Pediatrics, Children's Hospital, University of Colorado Medical Center, Denver, USA.
J Pharmacol Exp Ther. 1995 Jul;274(1):29-33.
An LLC-PK1 cell culture model was used to evaluate for a direct protective effect of the pentoxifylline analogue HWA-448 in gentamicin nephrotoxicity at the cellular level. Cells exposed to 2 mM gentamicin for 6 days displayed a significant decrease in specific activities of leucine aminopeptidase, NaK ATPase, and N-acetyl glucosaminidase, and an increase in total cellular phospholipids (P < .05). Concomitant exposure to 0.125 mM HWA-448, a dose that did not alter cellular enzymes or total phospholipids under physiologic conditions, prevented the alterations in marker enzymes and total phospholipids induced by gentamicin (P < .05). Gentamicin binding and uptake studies revealed 0.125 mM HWA-448 had no effect on LLC-PK1 cell plasma membrane binding or cellular gentamicin uptake. We conclude that HWA-448 ameliorates gentamicin-induced alterations in LLC-PK1 cell enzymes and phospholipids by a mechanism independent of plasma membrane binding or cellular uptake.
采用LLC - PK1细胞培养模型在细胞水平评估己酮可可碱类似物HWA - 448对庆大霉素肾毒性的直接保护作用。暴露于2 mM庆大霉素6天的细胞，其亮氨酸氨肽酶、钠钾ATP酶和N - 乙酰葡糖胺酶的比活性显著降低，细胞总磷脂增加（P < 0.05）。同时暴露于0.125 mM HWA - 448（该剂量在生理条件下不会改变细胞酶或总磷脂）可防止庆大霉素诱导的标记酶和总磷脂的改变（P < 0.05）。庆大霉素结合和摄取研究表明，0.125 mM HWA - 448对LLC - PK1细胞质膜结合或细胞庆大霉素摄取没有影响。我们得出结论，HWA - 448通过一种独立于质膜结合或细胞摄取的机制改善庆大霉素诱导的LLC - PK1细胞酶和磷脂的改变。
