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壳聚糖和姜黄素纳米颗粒在羟基磷灰石纳米颗粒经口摄取后对大鼠胃组织遗传毒性和炎症反应改善作用的生物评价

Bio-evaluation of the role of chitosan and curcumin nanoparticles in ameliorating genotoxicity and inflammatory responses in rats' gastric tissue followed hydroxyapatite nanoparticles' oral uptake.

作者信息

Mosa Israa F, Abd Haitham H, Abuzreda Abdelsalam, Assaf Nadhom, Yousif Amenh B

机构信息

Department of Biological Science and Animal Physiology, Institute of Graduate Studies and Research, Alexandria University, Egypt.

Department of Health, Safety and Environment (HSE), Arabian Gulf Oil Company (AGOCO), Benghazi, Libya.

出版信息

Toxicol Res (Camb). 2020 Aug 3;9(4):493-508. doi: 10.1093/toxres/tfaa054. eCollection 2020 Jul.

Abstract

Hydroxyapatite has been extensively used in tissue engineering due to its osteogenic potency, but its present toxicological facts are relatively insufficient. Here, the possible gastric toxicity of hydroxyapatite nanoparticles was evaluated biochemically to determine oxidant and antioxidant parameters in rats' stomach tissues. At results, hydroxyapatite nanoparticles have declined stomach antioxidant enzymes and reduced glutathione level, while an induction in lipid peroxidation and nitric oxide has been observed. Furthermore, DNA oxidation was analyzed by the suppression of toll-like receptors 2, nuclear factor-kappa B and Forkhead box P3 gene expression and also 8-Oxo-2'-deoxyguanosine level as a genotoxicity indicator. Various pro-inflammatory gene products have been identified that intercede a vital role in proliferation and apoptosis suppression, among these products: tumor suppressor p53, tumor necrosis factor-α and interliukin-6. Moreover, the hydroxyapatite-treated group revealed wide histological alterations and significant elevation in the number of proliferating cell nuclear antigen-positive cells, which has been observed in the mucosal layer of the small intestine, and these alterations are an indication of small intestine injury, while the appearance of chitosan and curcumin nanoparticles in the combination group showed improvement in all the above parameters with inhibition of toxic-oxidant parameters and activation of antioxidant parameters.

摘要

羟基磷灰石因其成骨能力而在组织工程中得到广泛应用,但其目前的毒理学事实相对不足。在此,通过生物化学方法评估了羟基磷灰石纳米颗粒可能的胃毒性,以确定大鼠胃组织中的氧化和抗氧化参数。结果显示,羟基磷灰石纳米颗粒降低了胃抗氧化酶和还原型谷胱甘肽水平,同时观察到脂质过氧化和一氧化氮增加。此外,通过抑制Toll样受体2、核因子-κB和叉头框P3基因表达以及作为遗传毒性指标的8-氧代-2'-脱氧鸟苷水平来分析DNA氧化。已鉴定出多种促炎基因产物在增殖和凋亡抑制中起重要作用,其中包括:肿瘤抑制因子p53、肿瘤坏死因子-α和白细胞介素-6。此外,羟基磷灰石处理组显示出广泛的组织学改变,并且在小肠粘膜层观察到增殖细胞核抗原阳性细胞数量显著增加,这些改变表明小肠受到损伤,而壳聚糖和姜黄素纳米颗粒组合组的上述所有参数均有改善,同时抑制了毒性氧化参数并激活了抗氧化参数。

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