Inhibition of mitochondrial complex I by various non-steroidal anti-inflammatory drugs and its protection by quercetin via a coenzyme Q-like action

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