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白藜芦醇及其纳米晶体:癌症治疗的有前途方法?

Resveratrol and its nanocrystals: A promising approach for cancer therapy?

机构信息

Agency for Medicinal Products and Medical Devices, Ksaverska cesta 4, HR-10000 Zagreb, Croatia.

Division of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, HR-10000 Zagreb, Croatia.

出版信息

Toxicol Appl Pharmacol. 2022 Jan 15;435:115851. doi: 10.1016/j.taap.2021.115851. Epub 2021 Dec 29.

Abstract

There has been a significant research interest in nanocrystals as a promising technology for improving the therapeutic efficacy of poorly water-soluble drugs, such as resveratrol. Little is known about the interaction of nanocrystals with biological tissue. The aim of this study was to investigate the potential use of resveratrol (RSV) and its nanocrystals (NANO-RSV) as antitumor agents in Ehrlich ascites tumour (EAT)-bearing mice and the interaction of nanocrystals with biological tissue through biochemical and histological changes of kidney, liver and EAT cells. After intraperitoneal injection of 2.5 × 10 cells into the abdominal cavity of mice, treatment of animals was started next day by injecting RSV or NANO-RSV at a dose of either 25 or 50 mg/kg every other day for 14 days. The results show that the administration of resveratrol and its nanocrystals lead to significant reductions in the proliferation of tumour cells in the abdominal cavity, and a reduction of the number of blood vessels in the peritoneum, with low systemic toxicity. In histopathological examinations, greater hepatocellular necrosis and apoptosis, hepatic fibrosis around the central vein and degeneration with minor fatty change were observed with RSV than with NANO-RSV. Inflammation with proximal tubular necrosis and renal glomerulus swelling were also observed, together with slight elevation of several biochemical parameters in both the RSV and NANO-RSV groups. In order to increase the beneficial effects and reduce risks associated with resveratrol nanocrystals, additional factors such as dose, genetic factors, health status, and the nature of the target cells should also be considered.

摘要

人们对纳米晶体作为提高疏水性差的药物(如白藜芦醇)治疗效果的有前途的技术产生了浓厚的研究兴趣。目前对于纳米晶体与生物组织的相互作用知之甚少。本研究旨在探讨白藜芦醇(RSV)及其纳米晶体(NANO-RSV)作为艾氏腹水瘤(EAT)荷瘤小鼠抗肿瘤药物的潜在用途,以及纳米晶体通过肾、肝和 EAT 细胞的生化和组织学变化与生物组织的相互作用。将 2.5×10 个细胞经腹腔注射入小鼠腹腔后,次日开始通过腹腔内注射 RSV 或 NANO-RSV(剂量分别为 25 或 50mg/kg),每隔一天进行一次,共 14 天,对动物进行治疗。结果表明,白藜芦醇及其纳米晶体的给药可显著减少腹腔内肿瘤细胞的增殖,并减少腹膜中的血管数量,且全身毒性低。在组织病理学检查中,与 NANO-RSV 相比,RSV 导致肝实质细胞坏死和凋亡增加,中央静脉周围肝纤维化以及轻微脂肪变性的退行性变。还观察到炎症伴有近端肾小管坏死和肾小球肿胀,同时在 RSV 和 NANO-RSV 组中观察到几个生化参数的轻微升高。为了提高白藜芦醇纳米晶体的有益效果并降低相关风险,还应考虑其他因素,如剂量、遗传因素、健康状况和靶细胞的性质。

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