期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 199, 期 1, 页码 18-28出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2012.05.006
关键词
NSAIDs; Mitochondria; Complex I; Ubiquinone; Electron transporting chain; Quercetin
资金
- Chilean National Science and Technology Commission through Fondef [VIU110015]
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 mu M) or to Caco-2 cells (250 mu M). 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 mu M). 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 mu M) protected against such inhibition, in a concentration dependent manner. In the case of aspirin, quercetin (5 mu M) increased the IC50 by 10-fold. In addition, the present study shows that quercetin (5-10 mu M) 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. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
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