Morphological and biochemical effects of gentamicin and cyclosporin-A on urinary cell phospholipids and phospholipases in man.

Morphological and biochemical effects of gentamicin and cyclosporin-A on urinary cell phospholipids and phospholipases in man.
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庆大霉素和环孢菌素 A 对人体尿细胞磷脂和磷脂酶的形态和生化影响。

DOI:
10.1002/jbt.2570030106
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发表时间:
1988
期刊:
Journal of biochemical toxicology
影响因子:
--
通讯作者:
Bose,S
Bose,S
中科院分区:
--
文献类型:
--
作者:
Chatterjee,S;Bose,S

文献摘要

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研究了鞘磷脂酶(E.C. 3.1.4.12)和磷脂酶A(E. C. 3.1.1.32)和C(E.C. 3.1.4.3)在来自四名正常受试者、四名接受庆大霉素(G)的患者和四名接受环孢菌素A(CsA)的患者的尿细胞中进行了研究。我们报告了接受G和CsA治疗的患者近端肾小管细胞的异常尿排泄。在接受G和接受CsA的患者的近端肾小管细胞的细胞质中发现膜封闭的嗜苏丹物质和许多空泡。接受G治疗的患者的磷脂酰胆碱(PC)、磷脂酰乙醇胺(PE)和鞘磷脂(SM)水平相对于正常水平分别为78%、38%和30%。与此相反,磷脂酰肌醇(PI)和PC的排泄分别降低50%和30%,在接受CsA的患者相比,控制。然而,这些患者的尿肾小管细胞中鞘磷脂水平中度升高,接受G和CsA的患者的细胞中酸性鞘磷脂酶的活性是正常水平的一半。最显著的结果是接受G.相反,接受CsA的患者中性鞘磷脂酶的活性与对照组相似。在接受G和CsA治疗的患者中,尿近端肾小管细胞中磷脂酶A活性分别降低和增加35%和15%。我们得出结论,在接受庆大霉素治疗的患者中,中性鞘磷脂酶活性缺乏先于磷脂(PL)过载和大体病理变化,而在接受环孢素A治疗的患者中则不然。
The morphology, lipid composition, and activity of sphingomyelinase (E.C. 3.1.4.12) and phospholipases A (E.C. 3.1.1.32) and C (E.C. 3.1.4.3) were studied in the urinary cells from four normal subjects, four patients receiving gentamicin (G), and four patients receiving cyclosporin‐A (CsA). We report that abnormal urinary excretion of proximal tubular cells occurred in patients receiving G and CsA. Membrane‐enclosed sudanophilic material and numerous vacuoles were found in the cytoplasm of the proximal tubular cells from both patients receiving G and those receiving CsA. Patients receiving G shed higher levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and sphingomyelin (SM) in the order of 78%, 38%, and 30% relative to normal. In contrast, the excretions of phosphatidylinositol (PI) and PC were 50% and 30% lower, respectively, in patients receiving CsA as compared to control. Sphingomyelin levels, however, were moderately elevated in these patients' urinary renal tubular cells.The activity of acid sphingomyelinase was one half the normal level in the cells of patients receiving G and CsA. The most striking result was a tenfold decrease in the activity of neutral sphingomyelinase in patients receiving G. In contrast, the activity of neutral sphingomyelinase in patients receiving CsA was similar to control. Phospholipase A activity was decreased and increased 35% and 15%, respectively, in urinary proximal tubular cells from patients receiving G and CsA.We conclude that deficient neutral sphingomyelinase activity precedes phospholipid (PL) overloading and gross pathological changes in patients receiving gentamicin but not in patients receiving cyclosporin‐A.