研究 WS2 纳米片对小鼠肠道的口服毒性:病理损伤、微量元素平衡、脂质变化和自噬。

IF 2.7 4区 医学 Q3 TOXICOLOGY Journal of Applied Toxicology Pub Date : 2024-09-29 DOI:10.1002/jat.4701
Zhenghao Zha, Sihuan Luo, Lianghuan Wei, Feixing Li, Youwen Li, Yi Cao
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引用次数: 0

摘要

石墨烯氧化物的成功为开发新型二维纳米材料(NMs)赢得了广泛的研究兴趣。WS2 纳米片(NSs)是一种新型过渡金属基二维纳米材料,但其毒性尚不清楚。本研究调查了 WS2 纳米片对小鼠肠道的口服毒性。雄性小鼠经胃内途径口服载体、1、10 或 100 mg/kg NSs,每天一次,连续 5 天。结果表明,NSs 不会引起肠道病理或超微结构变化。微量元素的变化极小,接触不会引起 W 的积累,只有 Co 的含量会随剂量增加而增加。各组小鼠都观察到了脂滴,但脂质组学数据表明,WS2 NSs 只显著减少了四种脂质,均属于磷脂酰胆碱(PC)。调节自噬脂肪分解的蛋白质,即 LC3、溶酶体相关膜蛋白 2(LAMP2)和过脂素 2(PLIN2)的水平均有所升高,但只有 LC3 有显著的统计学差异。本研究结果表明,反复胃内暴露于 WS2 NSs 只会对小鼠肠道的病理损伤、微量元素平衡、自噬和脂质谱产生极小的影响,表明 WS2 NSs 通过口服途径对小鼠肠道的生物相容性相对较高。
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Investigation of oral toxicity of WS2 nanosheets to mouse intestine: Pathological injury, trace element balance, lipid profile changes, and autophagy.

The success of graphene oxides has gained extensive research interests in developing novel 2D nanomaterials (NMs). WS2 nanosheets (NSs) are novel transition metal-based 2D NMs, but their toxicity is unclear. In this study, we investigated the oral toxicity of WS2 NSs to mouse intestines. Male mice were administrated with vehicles, 1, 10, or 100 mg/kg NSs via intragastric route, once a day, for 5 days. The results indicate that the NSs did not induce pathological or ultrastructural changes in intestines. There were minimal changes of trace elements that the exposure did not induce W accumulation, and only Co levels were dose-dependently increased. Lipid droplets were observed in all groups of mice, but lipidomics data indicate that WS2 NSs only significantly decreased four lipid species, all belonging to phosphatidylcholine (PC). The levels of proteins regulating autophagic lipolysis, namely, LC3, lysosomal associated membrane protein 2 (LAMP2) and perilipin 2 (PLIN2), were increased, but it was only statistically significantly different for LC3. The results of this study suggest that repeated intragastric exposure to WS2 NSs only induced minimal influences on pathological injury, trace element balance, autophagy, and lipid profiles in mouse intestines, indicating relatively high biocompatibility of WS2 NSs to mouse intestine via oral route.

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来源期刊
CiteScore
7.00
自引率
6.10%
发文量
145
审稿时长
1 months
期刊介绍: Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.
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