Molecular mechanisms of gastrointestinal protection by quercetin against indomethacin-induced damage: role of NF-κB and Nrf2

详细信息    查看全文

• 作者：Catalina Carrasco-Pozo^a ; ^{catalinacarrasco@med.uchile.cl" class="auth_mail" title="E-mail the corresponding author} ; Rodrigo L. Castillo^b ; Caroll Beltrá ; n^c ; Alfonso Miranda^c ; Jocelyn Fuentes^d ; Martin Gotteland^a ; ^d
• 关键词：EMSA ; electrophoretic mobility shift assay ; GCLC ; glutamate-cysteine ligase catalytic subunit ; GI ; gastrointestinal ; GSHpx ; glutathione peroxidase ; ICAM-1 ; intercellular adhesion molecule-1 ; IkBα ; inhibitory subunit of kappa B ; INDO ; indomethacin ; MAPK ; mitogen activated protein kinase ; MPO ; myeloperoxidase ; NF-κB ; nuclear transcription factor kappa B ; Nrf2 ; nuclear factor (erythroid-derived 2)-like 2 ; NSAID ; nonsteroidal antiinflammatory drug ; NQO1 ; NAD(P)H dehydrogenase [quinone] 1 ; O2° ; &mi
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：27
• 期：Complete
• 页码：289-298
• 全文大小：1077 K

文摘

The aim of this study was to determine the gastrointestinal protection by quercetin against indomethacin-induced oxidative stress and inflammation, with specific interest in studying the underlying molecular mechanisms. We hypothesized that the quercetin-protective effect relies on its antioxidant and antiinflammatory properties. Rats were pretreated with quercetin (50- or 100-mg/kg, ig single dose), 30 min before INDO administration (40-mg/kg ig single dose). Caco-2 cells were treated with INDO (250 and 500 μM) in the absence or presence of quercetin (10 μg/ml). Quercetin prevented the decrease in nuclear translocation of Nrf2, a key regulator of the antioxidant response, and the increase in reactive oxygen species levels induced by INDO by inhibiting the enhancement of NADPH oxidase and xanthine oxidase activities as well as the reduction in superoxide dismutase and glutathione peroxidase activities in gastric and ileal tissues. Quercetin also prevented INDO-induced ICAM-1 and P-selectin expressions and the increase of myeloperoxidase activity in gastric and ileal tissues and NF-κB activation and IL-8 production in Caco-2 cells. Quercetin did not affect the inhibition of TNFα-mediated production of prostaglandin E₂ induced by INDO in Caco-2 cells. The protective effects of quercetin observed in the gastric and ileal mucosa of rats as well as in Caco-2 cells relied on the ability of this flavonol to prevent NF-κB activation and increase Nrf2 translocation. This study supports the concept that quercetin may be useful in the prevention and/or treatment of nonsteroidal antiinflammatory drug-associated side effects, without interfering with their therapeutic efficacy.