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摄入的纳米纤维素在体外肠上皮细胞和体内大鼠模型中的毒理学效应。

Toxicological effects of ingested nanocellulose in in vitro intestinal epithelium and in vivo rat models.

作者信息

DeLoid Glen M, Cao Xiaoqiong, Molina Ramon M, Silva Daniel Imbassahy, Bhattacharya Kunal, Ng Kee Woei, Loo Say Chye Joachim, Brain Joseph D, Demokritou Philip

机构信息

Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.

School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798.

出版信息

Environ Sci Nano. 2019 Jul 1;6(7):2105-2115. doi: 10.1039/c9en00184k. Epub 2019 Jun 18.

Abstract

Cellulose is widely used as a thickener and filler in foods and drugs. It has been designated "generally regarded as safe" (GRAS). Nanocellulose (NC) has many additional potential applications designed to improve food quality and safety, but has not yet been designated as GRAS. Here we present results of toxicological studies of ingested NC in physiologically relevant and systems. studies employed a gastrointestinal tract simulator to digest two widely-used forms of NC, nanocellulose fibrils (CNF) and cellulose nanocrystals (CNC), at 0.75 and 1.5% w/w, in a fasting diet as well as in a standardized food model based on the average American diet. A triculture model of small intestinal epithelium was used to assess effects of a 24-hour incubation with the digested products (digesta) on cell layer integrity, cytotoxicity and oxidative stress. Other than a 10% increase over controls in reactive oxygen species (ROS) production with 1.5% w/w CNC, no significant changes in cytotoxicity, ROS or monolayer integrity were observed. toxicity was evaluated in rats gavaged twice weekly for five weeks with 1% w/w suspensions of CNF in either water or cream. Blood, serum, lung, liver, kidney, and small intestine were collected for analysis. No significant differences in hematology, serum markers or histology were observed between controls and rats given CNF suspensions. These findings suggest that ingested NC has little acute toxicity, and is likely non-hazardous when ingested in small quantities. Additional chronic feeding studies are required to assess long term effects, and potential detrimental effects on the gut microbiome and absorbance of essential micronutrients. These studies are underway, and their outcome will be reported in the near future.

摘要

纤维素在食品和药品中被广泛用作增稠剂和填充剂。它已被指定为“一般认为安全”(GRAS)。纳米纤维素(NC)有许多旨在改善食品质量和安全性的潜在应用,但尚未被指定为GRAS。在此,我们展示了在生理相关系统中摄入NC的毒理学研究结果。研究采用胃肠道模拟器,在禁食饮食以及基于美国平均饮食的标准化食品模型中,以0.75%和1.5%(w/w)的比例消化两种广泛使用的NC形式,即纳米纤维素原纤维(CNF)和纤维素纳米晶体(CNC)。使用小肠上皮的三培养模型来评估与消化产物(消化物)进行24小时孵育对细胞层完整性、细胞毒性和氧化应激的影响。除了1.5%(w/w)的CNC使活性氧(ROS)产生量比对照组增加10%外,未观察到细胞毒性、ROS或单层完整性有显著变化。通过每周两次给大鼠灌胃为期五周的1%(w/w)CNF水悬液或乳膏悬液来评估其毒性。收集血液、血清、肺、肝、肾和小肠进行分析。在对照组和给予CNF悬液的大鼠之间,未观察到血液学、血清标志物或组织学有显著差异。这些发现表明,摄入的NC几乎没有急性毒性,少量摄入时可能无危害。需要进行额外的长期喂养研究来评估长期影响以及对肠道微生物群和必需微量营养素吸收的潜在有害影响。这些研究正在进行中,其结果将在不久的将来报告。

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