Nextcea, Inc., 600 West Cummings Park, #6375, Woburn, MA 01801, USA.
Expert Opin Drug Metab Toxicol. 2010 May;6(5):555-70. doi: 10.1517/17425251003601961.
Drug-induced phospholipidosis (PL) is a phospholipid storage disorder characterized by the accumulation of multi-lamellar bodies (myeloid bodies) in tissues. A major unanswered question is whether PL represents a benign adaptive response, symptom or early event in drug toxicity. The absence of a non-invasive biomarker to monitor tissue PL has made it difficult to determine the prevalence and implications of PL in the clinic. As a result, the interpretation of PL in risk assessment remains uncertain in preclinical and clinical drug development.
This review describes the rationale for bis(monoacylglycerol)phosphate (BMP) as a biomarker of PL and explores the potential links between PL and the toxicities of drugs.
The similarities between the hypothesized roles of BMP in PL and Niemann-Pick type C disease are discussed. The potential implications of PL for cellular function are described in the context of drug-induced QT prolongation, myopathy and renal toxicity.
A specific species of BMP, di-docosahexaenoyl-BMP, should be investigated further as a non-invasive biomarker to monitor the onset and time course of PL and to better understand the functional consequences which could contribute to the toxicities of drugs.
药物诱导的磷脂病（PL）是一种以组织中多膜小体（骨髓小体）积累为特征的磷脂储存障碍。一个主要的未解决的问题是 PL 是否代表药物毒性的良性适应性反应、症状或早期事件。由于缺乏监测组织 PL 的非侵入性生物标志物，因此难以确定 PL 在临床上的普遍性和意义。因此，PL 在临床前和临床药物开发中的风险评估中的解释仍然不确定。
本文描述了双（单酰基甘油）磷酸（BMP）作为 PL 生物标志物的基本原理，并探讨了 PL 与药物毒性之间的潜在联系。
讨论了 BMP 在 PL 中的假设作用与尼曼-匹克 C 型疾病之间的相似性。在药物诱导的 QT 延长、肌病和肾毒性的背景下，描述了 PL 对细胞功能的潜在影响。
应进一步研究特定的 BMP 物种，即双二十二碳六烯酰基-BMP，作为一种非侵入性生物标志物，以监测 PL 的发生和时间过程，并更好地了解可能导致药物毒性的功能后果。
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