کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2602692 1133794 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nimesulide interaction with membrane model systems: Are membrane physical effects involved in nimesulide mitochondrial toxicity?
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Nimesulide interaction with membrane model systems: Are membrane physical effects involved in nimesulide mitochondrial toxicity?
چکیده انگلیسی

Nimesulide (NIM), a widely used nonsteroidal anti-inflammatory drug (NSAID), is known to interfere with mitochondrial physiology and to cause idiosyncratic hepatotoxicity. In this study, we characterized the effects of NIM on the physical properties of membrane models containing the main phospholipid classes of the inner mitochondrial membrane: phosphatidylcholine (PC), phosphatidylethanolamine (PE) and cardiolipin (CL). NIM binding/incorporation was observed with the mitochondrial membrane mimicking model composed of dioleoyl PC (DOPC), dioleoyl PE (DOPE) and tetraoleoyl CL (TOCL) at a 1:1:1 M ratio, as well as an increase of membrane permeability, monitored by calcein release, and an increase of lipid disorder, evaluated by fluorescence anisotropy of DPH-PA. Consistently, DSC thermograms of dipalmitoyl PC (DPPC) and a mixture of dipalmitoyl PE (DPPE) and TOCL (7:3 M ratio) showed a NIM-induced decrease of the cooperativity of the phase transition and a shift of the DPPC endotherm to lower temperatures. On the other hand, 31P NMR studies with the ternary lipid model indicated a stabilizing effect of NIM on the lipid bilayer structure. Quenching of the fluorescent probes DPH and DPH-PA revealed a peripheral insertion of NIM in the hydrophobic portion of the bilayer. Our data indicate that NIM may influence mitochondria physiological processes by interfering with membrane structure and dynamics. The relevance of these findings will be discussed in terms of the reported NIM effects on mitochondria transmembrane potential, protonophoresis, and induction of the permeability transition pore.


► Nimesulide perturbs mitochondrial membrane mimicking lipid models (Mit models).
► Nimesulide binds to lipid vesicles, promotes lipid disorder and calcein release.
► Nimesulide counteracts the La-HII phase transition in Mit models plus Ca2+.
► Nimesulide quenches both DPH and DPH-PA incorporated in Mit models.
► Nimesulide-induced membrane disturbance may concur to mitochondria disfunction.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 25, Issue 6, September 2011, Pages 1215–1223
نویسندگان
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