کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2580725 1130152 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of mitochondrial complex I by various non-steroidal anti-inflammatory drugs and its protection by quercetin via a coenzyme Q-like action
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Inhibition of mitochondrial complex I by various non-steroidal anti-inflammatory drugs and its protection by quercetin via a coenzyme Q-like action
چکیده انگلیسی

Mitochondrial dysfunction plays a major role in the development of oxidative stress and cytotoxicity induced by non-steroidal anti-inflammatory drugs (NSAIDs). A major objective of the present study was to investigate whether in vitro the NSAIDs, aspirin, indomethacin, diclofenac, piroxicam and ibuprofen, which feature different chemical structures, are able to inhibit mitochondrial complex I. All NSAIDs were effective inhibitors when added both, directly to mitochondria isolated from rat duodenum epithelium (50 μM) or to Caco-2 cells (250 μM). In the former system, complex I inhibition was concentration-dependent and susceptible to competition and reversion by the addition of coenzyme Q (32.5–520 μM). Based on reports suggesting a potential gastro-protective activity of quercetin, the ability of this flavonoid to protect isolated mitochondria against NSAIDs-induced complex I inhibition was evaluated. Low micromolar concentrations of quercetin (1–20 μM) protected against such inhibition, in a concentration dependent manner. In the case of aspirin, quercetin (5 μM) increased the IC50 by 10-fold. In addition, the present study shows that quercetin (5–10 μM) can behave as a “coenzyme Q-mimetic” molecule, allowing a normal electron flow along the whole electron transporting chain (complexes I, II, III and IV). The exposed findings reveal that complex I inhibition is a common deleterious effect of NSAIDs at the mitochondrial level, and that such effect is, for all tested agents, susceptible to be prevented by quercetin. Data provided here supports the contention that the protective action of quercetin resides on its, here for first time-shown, ability to behave as a coenzyme Q-like molecule.


► Inhibition of mitochondrial complex I is a common effect of NSAIDs.
► Complex I inhibition induced by NSAIDs is competable and reversible by coenzyme Q.
► Quercetin protects mitochondria against complex I inhibition induced by NSAIDs.
► Quercetin behaves as a “coenzyme Q mimetic” at the electron transporting chain.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 199, Issue 1, 30 July 2012, Pages 18–28
نویسندگان
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