کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2570895 1128607 2009 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations
چکیده انگلیسی

AimsOur goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved.MethodsCSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca2+]i was measured by flow cytometry using fluo-3. Mitochondrial [Ca2+] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified by dichlorofluorescein (DCF) fluorescence with confocal microscopy.ResultsCSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca2+ uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca2+]i in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca2+]i during P-MI was also prevented by ranolazine.ConclusionsCSE in clinically relevant concentrations increases myocyte [Ca2+]i during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 236, Issue 1, 1 April 2009, Pages 71–77
نویسندگان
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