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一种混合价态多氧钒酸盐簇合物的体外、口服急性及28天重复口服剂量毒性研究

In Vitro, Oral Acute, and Repeated 28-Day Oral Dose Toxicity of a Mixed-Valence Polyoxovanadate Cluster.

作者信息

Barbosa Mariana de M, Lima Lidiane M A de, Alves Widarlane A da S, Lima Eucilene K B de, Silva Luzia A da, Silva Thiago D da, Postal Kahoana, Ramadan Mohammad, Kostenkova Kateryna, Gomes Dayane A, Nunes Giovana G, Pereira Michelly C, Silva Wagner E da, Belian Mônica F, Crans Debbie C, Lira Eduardo C

机构信息

Centro de Biociências, Departamento de Fisiologia e Farmacologia, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil.

Departamento de Química, Universidade Federal Rural de Pernambuco, Recife 52171-900, PE, Brazil.

出版信息

Pharmaceuticals (Basel). 2023 Aug 30;16(9):1232. doi: 10.3390/ph16091232.

Abstract

Polyoxovanadates (POV) are a subgroup of polyoxometalates (POM), which are nanosized clusters with reported biological activities. This manuscript describes the first toxicity evaluation of a mixed-valence polyoxovanadate, pentadecavanadate, (MeN)[VOCl], abbreviated as V. Cytotoxicity experiments using peripheral blood mononuclear cells (PBMC), larvae of Leach, and in vivo oral acute and repeated 28-day doses in mice was carried out. The LC values in PBMC cells and were 17.5 ± 5.8 μmol L, and 17.9 µg L, respectively, which indicates high cytotoxic activity. The toxicity in mice was not observed upon acute exposure in a single dose, however, the V repeated 28-day oral administration demonstrated high toxicity using 25 mg/kg, 50 mg/kg and, 300 mg/kg doses. The biochemical and hematological analyses during the 28-day administration of V showed significant alteration of the metabolic parameters related to the kidney and liver, suggesting moderate toxicity. The V toxicity was attributed to the oxidative stress and lipid peroxidation, once thiobarbituric acid (TBAR) levels significantly increased in both males and females treated with high doses of the POV and also in males treated with a lower dose of the POV. This is the first study reporting a treatment-related mortality in animals acutely administrated with a mixed-valence POV, contrasting with the well-known, less toxic decavanadate. These results document the toxicity of this mixed-valence POV, which may not be suitable for biomedical applications.

摘要

多氧钒酸盐(POV)是多金属氧酸盐(POM)的一个亚组,多金属氧酸盐是具有已报道生物活性的纳米级簇。本手稿描述了一种混合价多氧钒酸盐——十五钒酸盐(MeN)[VOCl],简称为V的首次毒性评估。使用外周血单核细胞(PBMC)、Leach幼虫进行了细胞毒性实验,并对小鼠进行了体内口服急性和重复28天剂量实验。PBMC细胞中的LC值分别为17.5±5.8μmol/L和17.9μg/L,这表明其具有高细胞毒性活性。单次急性暴露于小鼠时未观察到毒性,然而,V重复28天口服给药,使用25mg/kg、50mg/kg和300mg/kg剂量时显示出高毒性。在V的28天给药期间进行的生化和血液学分析表明,与肾脏和肝脏相关的代谢参数发生了显著变化,表明具有中度毒性。V的毒性归因于氧化应激和脂质过氧化,因为在用高剂量POV处理的雄性和雌性小鼠以及用低剂量POV处理的雄性小鼠中,硫代巴比妥酸(TBAR)水平均显著升高。这是第一项报道急性给予混合价POV与治疗相关死亡率的研究,这与众所周知的毒性较小的十钒酸盐形成对比。这些结果证明了这种混合价POV的毒性,其可能不适合生物医学应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/764d/10536805/fc14926b9a93/pharmaceuticals-16-01232-g001.jpg

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