Membrane permeabilization by non-steroidal anti-inflammatory drugs
Membrane permeabilization by non-steroidal anti-inflammatory drugs
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DOI：
10.1016/j.bbrc.2004.08.205
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发表时间：
2004-10-22
影响因子：
3.1
通讯作者：
Mizushima, T
中科院分区：
文献类型：
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作者：
Tomisato, W;Tanaka, K;Mizushima, T
非甾体抗炎药（NSAID）的细胞毒性参与NSAID诱导的胃病变的形成。然而，这些细胞毒性作用背后的机制尚未完全了解。我们发现，当使用浓度与导致细胞毒性的浓度相似时，测试的几种NSAID会引起溶血。此外，发现这些相同的非甾体抗炎药可直接渗透负载钙黄绿素的脂质体的膜。鉴于NSAID浓度对细胞毒性和膜透化作用的相似性，这些NSAID的细胞毒性作用可能通过生物膜的透化介导。细胞内Ca2+水平的增加可导致细胞死亡。我们在此发现，所有测试的NSAID在与导致细胞毒性的浓度相似的浓度下增加细胞内Ca2+水平。基于这些结果，我们考虑了一种可能性，即膜透化的非甾体抗炎药诱导细胞死亡，通过增加细胞内Ca2+水平。(C)2004年爱思唯尔公司All rights reserved.
The cytotoxicity of non-steroidal anti-inflammatory drugs (NSAIDs) is involved in the formation of NSAID-induced gastric lesions. The mechanism(s) behind these cytotoxic effects, however, is not well understood. We found here that several NSAIDs tested caused hemolysis when employed at concentrations similar to those that result in cytotoxicity. Moreover, these same NSAIDs were found to directly permeabilize the membranes of calcein-loaded liposomes. Given the similarity in NSAID concentrations for cytotoxic and membrane permeabilization effects, the cytotoxic action of these NSAIDs may be mediated through the permeabilization of biological membranes. Increase in the intracellular Ca2+ level can lead to cell death. We here found that all of NSAIDs tested increased the intracellular Ca2+ level at concentrations similar to those that result in cytotoxicity. Based on these results, we consider a possibility that membrane permeabilization by NSAIDs induces cell death through increase in the intracellular Ca2+ level. (C) 2004 Elsevier Inc. All rights reserved.