Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, 100191, P.R. China.
Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University, Beijing, 100191, P.R. China.
Part Fibre Toxicol. 2023 Jun 22;20(1):24. doi: 10.1186/s12989-023-00535-9.
Titanium dioxide (TiO), no matter in nanoscale or micron sizes, has been widely used in food industry as additives for decades. Given the potential impact of TiO 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 TiO NPs on the course and prognosis of ulcerative colitis by oral gavaging TiO 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 TiO 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 TiO NPs exposure during the development phase of UC and the high dose (300 mg/kg) group of TiO 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 TiO 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 TiO NPs could affect the course of acute colitis in exacerbating the development of UC, prolonging the UC course and inhibiting UC recovery.
二氧化钛（TiO），无论纳米级还是微米级，几十年来一直被广泛用作食品工业中的添加剂。鉴于 TiO 对胃肠道上皮细胞和实质细胞（包括杯状细胞）的潜在影响，公众消费者可能会因 TiO 在食品中的广泛传播而面临疾病风险。因此，我们着手研究 TiO NPs 通过口服灌胃在结肠炎诱导（7 天，第 1 天至第 7 天）和恢复期（10 天，第 8 天至第 17 天）阶段以 0、30、100 和 300mg/kg 剂量水平给予 TiO NPs 对溃疡性结肠炎的病程和预后的影响。
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，TiO NPs 显著加重了 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）和结肠黏膜损伤指数（CMDI）评分，缩短了结肠长度，增加了结肠中的炎症浸润。TiO NPs 暴露在 UC 发展阶段的低剂量（30mg/kg）组和 UC 自愈合阶段的高剂量（300mg/kg）组中发生了最显著的变化。活性氧（ROS）水平升高和抗氧化酶（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））的上调表明 TiO NP 暴露在小鼠中引发了氧化应激。此外，caspase-1 mRNA 的上调和硫氧还蛋白相互作用蛋白（TXNIP）的表达增加进一步证明了 ROS-TXNIP-NLR 家族包含吡喃结构域 3（NLRP3）炎性体途径参与加重 UC 的发展。
口服摄入 TiO NPs 可影响急性结肠炎的病程，加重 UC 的发展，延长 UC 病程并抑制 UC 恢复。
