Toxicology and Applied Pharmacology ( IF 3.3 ) Pub Date : 2022-11-30 , DOI: 10.1016/j.taap.2022.116327 Xiaojia He 1 , Zachery R Jarrell 1 , Matthew Ryan Smith 2 , ViLinh Thi Ly 1 , Yongliang Liang 1 , Michael Orr 1 , Young-Mi Go 1 , Dean P Jones 1
Vanadium is a toxic metal listed by the IARC as possibly carcinogenic to humans. Manufactured nanosize vanadium pentoxide (V2O5) materials are used in a wide range of industrial sectors and recently have been developed as nanomedicine for cancer therapeutics, yet limited information is available to evaluate relevant nanotoxicity. In this study we used high-resolution metabolomics to assess effects of two V2O5 nanomaterials, nanoparticles and nanofibers, at exposure levels (0.01, 0.1, and 1 ppm) that did not cause cell death (i.e., non-cytotoxic) in a human airway epithelial cell line, BEAS-2B. As prepared, V2O5 nanofiber exhibited a fibrous morphology, with a width approximately 63 ± 12 nm and length in average 420 ± 70 nm; whereas, V2O5 nanoparticles showed a typical particle morphology with a size 36 ± 2 nm. Both V2O5 nanoparticles and nanofibers had dose-response effects on aminosugar, amino acid, fatty acid, carnitine, niacin and nucleotide metabolism. Differential effects of the particles and fibers included dibasic acid, glycosphingolipid and glycerophospholipid pathway associations with V2O5 nanoparticles, and cholesterol and sialic acid metabolism associations with V2O5 nanofibers. Examination by transmission electron microscopy provided evidence for mitochondrial stress and increased lysosome fusion by both nanomaterials, and these data were supported by effects on mitochondrial membrane potential and lysosomal activity. The results showed that non-cytotoxic exposures to V2O5 nanomaterials impact major metabolic pathways previously associated with human lung diseases and suggest that toxico-metabolomics may be useful to evaluate health risks from V2O5 nanomaterials.
中文翻译:
V2O5 纳米粒子和 V2O5 纳米纤维在人气道上皮 BEAS-2B 细胞中的代谢组学
钒是国际癌症研究机构 (IARC) 列为可能对人类致癌的有毒金属。制造的纳米五氧化二钒(V 2 O 5 )材料广泛应用于工业领域,最近已被开发为用于癌症治疗的纳米药物,但可用于评估相关纳米毒性的信息有限。在这项研究中,我们使用高分辨率代谢组学来评估两种 V 2 O 5纳米材料、纳米粒子和纳米纤维在暴露水平(0.01、0.1 和 1 ppm)下的影响,不会导致细胞死亡(即非细胞毒性)。人气道上皮细胞系 BEAS-2B。制备的V 2 O 5纳米纤维呈纤维状形貌,宽度约为63±12 nm,长度平均为420±70 nm。而V 2 O 5纳米颗粒表现出典型的颗粒形态,尺寸为36±2 nm。 V 2 O 5纳米颗粒和纳米纤维对氨基糖、氨基酸、脂肪酸、肉碱、烟酸和核苷酸代谢均具有剂量反应效应。颗粒和纤维的不同作用包括二元酸、鞘糖脂和甘油磷脂途径与V 2 O 5纳米颗粒的关联,以及胆固醇和唾液酸代谢与V 2 O 5纳米纤维的关联。透射电子显微镜检查提供了线粒体应激和两种纳米材料增加的溶酶体融合的证据,并且这些数据得到了对线粒体膜电位和溶酶体活性的影响的支持。 结果表明,V 2 O 5纳米材料的非细胞毒性暴露会影响先前与人类肺部疾病相关的主要代谢途径,并表明毒物代谢组学可能有助于评估 V 2 O 5纳米材料的健康风险。