Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin.
Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin.
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DOI：
10.1007/s00535-012-0564-5
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发表时间：
2012-09
影响因子：
6.3
通讯作者：
Okazaki, Kazuichi
中科院分区：
文献类型：
--
作者：
Nakajima, Atsushi;Fukui, Toshiro;Takahashi, Yu;Kishimoto, Masanobu;Yamashina, Masao;Nakayama, Shinji;Sakaguchi, Yutaku;Yoshida, Katsunori;Uchida, Kazushige;Nishio, Akiyoshi;Yodoi, Junji;Okazaki, Kazuichi
吲哚美辛是一种非甾体类抗炎药，其副作用常引起胃粘膜损伤。炎症细胞的浸润和激活、促炎细胞因子和趋化因子的产生、活性氧的产生以及凋亡信号的激活参与了吲哚美辛诱导的胃损伤的发病机制。我们研究了清酒酵母衍生的硫氧还蛋白（一种具有抗氧化活性和各种氧化还原调节功能的小氧化还原活性蛋白）是否减少吲哚美辛诱导的胃损伤。C57 BL/6小鼠腹腔注射吲哚美辛（40 mg/kg体重），造成胃损伤。在施用吲哚美辛之前，向小鼠提供含有非遗传修饰的清酒酵母衍生的硫氧还蛋白（硫氧还蛋白200 μg/g）的食物颗粒3天。对组织学检查、髓过氧化物酶活性评估以及促炎细胞因子和趋化因子（白细胞介素[IL]-1β、IL-6和CXCL 1）的基因表达分析进行了统计学评价。通过用100 μg/ml清酒酵母衍生的硫氧还蛋白预孵育1小时后，用200和400 μM吲哚美辛处理24小时诱导小鼠胃上皮GSM 06细胞释放乳酸脱氢酶来测定吲哚美辛的细胞毒性。通过含硫氧还蛋白的食物颗粒预处理，吲哚美辛诱导的肉眼（水肿、出血和溃疡）和组织学（坏死、粘膜下水肿、中性粒细胞浸润）结果显著减少。与未用含硫氧还蛋白的食物颗粒预处理的小鼠相比，这种预处理也显著降低了胃髓过氧化物酶活性和促炎细胞因子（IL-1β和IL-6）的基因表达。给予清酒酵母衍生的硫氧还蛋白显著降低了GSM 06细胞中吲哚美辛诱导的细胞毒性。我们的结论是，口服清酒酵母衍生的硫氧还蛋白减少吲哚美辛诱导的胃损伤。清酒酵母衍生的硫氧还蛋白可能对吲哚美辛诱导的胃损伤具有治疗潜力。
Indomethacin is one of the group of nonsteroidal anti-inflammatory drugs, which often cause gastric mucosal injury as a side effect. Infiltration and activation of inflammatory cells, production of proinflammatory cytokines and chemokines, generation of reactive oxygen species, and activation of apoptotic signaling are involved in the pathogenesis of indomethacin-induced gastric injury. We examined whether sake yeast-derived thioredoxin (a small redox-active protein with anti-oxidative activity and various redox-regulating functions) reduced indomethacin-induced gastric injury. Gastric injury was produced by the intraperitoneal administration of indomethacin (40 mg/kg body weight) to C57BL/6 mice. Prior to the administration of indomethacin, the mice were offered food pellets containing non-genetically modified sake yeast-derived thioredoxin (thioredoxin 200 μg/g) for 3 days. Histological examinations, assessment of myeloperoxidase activity, and analysis of the gene expressions of proinflammatory cytokines and a chemokine (interleukin [IL]-1β, IL-6, and CXCL1) were statistically evaluated. Indomethacin cytotoxicity was determined by lactate dehydrogenase release from murine gastric epithelial GSM06 cells induced by 24-h treatment with 200 and 400 μM indomethacin after 1-h preincubation with 100 μg/ml sake yeast-derived thioredoxin. Macroscopic (edema, hemorrhage, and ulcers) and histological (necrosis, submucosal edema, neutrophil infiltration) findings induced by indomethacin were significantly reduced by pretreatment with food pellets containing thioredoxin. Gastric myeloperoxidase activity and the gene expressions of proinflammatory cytokines (IL-1β and IL-6) were also significantly reduced by this pretreatment compared with findings in the mice not pretreated with thioredoxin-containing food pellets. The administration of sake yeast-derived thioredoxin significantly reduced indomethacin-induced cytotoxicity in GSM06 cells. We conclude that oral administration of sake yeast-derived thioredoxin reduces indomethacin-induced gastric injury. Sake yeast-derived thioredoxin may have therapeutic potential against indomethacin-induced gastric injury.
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影响因子：
37.8
作者：
Shioji, K;Kishimoto, C;Yodoi, J
通讯作者：
Yodoi, J
影响因子：
29.4
作者：
Beck, PL;Xavier, R;Seed, B
通讯作者：
Seed, B
DOI：
10.1073/pnas.96.7.4131
发表时间：
1999-03-30
影响因子：
11.1
作者：
Takagi, Y;Mitsui, A;Yodoi, J
通讯作者：
Yodoi, J
影响因子：
--
作者：
WALLACE, JL;KEENAN, CM;GRANGER, DN
通讯作者：
GRANGER, DN
影响因子：
--
作者：
ANDREWS, FJ;MALCONTENTIWILSON, C;OBRIEN, PE
通讯作者：
OBRIEN, PE