Titanium dioxide (TiO2), no matter in nanoscale or micron sizes, has been widely used in food industry as additives for decades. Given the potential impact of TiO2 on the gastrointestinal epithelial and parenchymal cells, including goblet cells, the public consumers may suffer the risk of diseases caused by its widespread dissemination in food products. We therefore set out to investigate the impact of TiO2 NPs on the course and prognosis of ulcerative colitis by oral gavaging TiO2 NPs at the doses levels of 0, 30, 100, and 300 mg/kg during the induction (7 days, from day 1 to day 7) and recovery (10 days, from day 8 to day 17) phases of colitis in mice. The ulcerative colitis (UC) disease model was established by administrating of 2.5% dextran sulfate sodium (DSS) solution. Our results show that TiO2 NPs significantly enhanced the severity of DSS-induced colitis, decreased the body weight, increased the disease activity index (DAI) and colonic mucosa damage index (CMDI) scores, shortened the colonic length, increased the inflammatory infiltration in the colon. The most significant changes occurred in the low dose (30 mg/kg) group of TiO2 NPs exposure during the development phase of UC and the high dose (300 mg/kg) group of TiO2 NPs during UC self-healing phase. Increased reactive oxygen species (ROS) level and upregulation of anti-oxidant enzymes including total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX) and catalase (CAT), demonstrate that the TiO2 NP exposure has triggered oxidative stress in mice. Moreover, the upregulation of caspase-1 mRNA and increased expression of thioredoxin interacting protein (TXNIP) further demonstrate the involvement of the ROS-TXNIP-NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in aggravating the development of UC. Oral intake of TiO2 NPs could affect the course of acute colitis in exacerbating the development of UC, prolonging the UC course and inhibiting UC recovery.

中文翻译：

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口服二氧化钛纳米颗粒影响小鼠溃疡性结肠炎的病程和预后：ROS-TXNIP-NLRP3炎症小体通路的参与

二氧化钛（TiO2），无论是纳米级还是微米级尺寸，几十年来一直作为添加剂广泛应用于食品工业。鉴于二氧化钛对胃肠道上皮细胞和实质细胞（包括杯状细胞）的潜在影响，公众消费者可能会面临因其在食品中广泛传播而引起疾病的风险。因此，我们着手研究 TiO2 NPs 对溃疡性结肠炎病程和预后的影响，方法是在诱导期间（7 天，从第 1 天开始）口服 TiO2 NPs，剂量水平为 0、30、100 和 300 mg/kg。小鼠结肠炎的第 7 天）和恢复（10 天，第 8 天到第 17 天）阶段。通过给予2.5%葡聚糖硫酸钠(DSS)溶液建立溃疡性结肠炎(UC)疾病模型。我们的结果表明，TiO2 NPs 显着增强了 DSS 诱导的结肠炎的严重程度，降低了体重，增加了疾病活动指数（DAI）和结肠粘膜损伤指数（CMDI）评分，缩短了结肠长度，增加了结肠中的炎症浸润。冒号。最显着的变化发生在UC发展阶段的低剂量（30 mg/kg）TiO2 NPs暴露组和UC自愈阶段的高剂量（300 mg/kg）TiO2 NPs暴露组。活性氧 (ROS) 水平增加和抗氧化酶（包括总超氧化物歧化酶 (T-SOD)、谷胱甘肽过氧化物酶 (GSH-PX) 和过氧化氢酶 (CAT)）上调，表明 TiO2 NP 暴露引发了小鼠的氧化应激。而且，caspase-1 mRNA的上调和硫氧还蛋白相互作用蛋白（TXNIP）表达的增加进一步证明了ROS-TXNIP-NLR家族pyrin结构域3（NLRP3）炎性体途径参与了加重UC的发展。口服TiO2 NPs可影响急性结肠炎的病程，加剧UC的发展、延长UC病程并抑制UC恢复。