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Preliminary evaluation of the cytotoxic and genotoxic potential of D-003: Mixture of very long chain fatty acids.

机译:D-003的细胞毒性和遗传毒性的初步评估:超长链脂肪酸的混合物。

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D-003 is a mixture of very long chain aliphatic acids purified from sugar cane wax, wherein octacosanoic acid represents the major component. Previous experimental studies have shown that D-003 inhibits platelet aggregation in rodents. Also, its lowers total (TC) and low-density lipoprotein cholesterol (LDL-C) in normocholesterolemic rabbits in a dose-dependent manner and inhibits cholesterol biosynthesis in fibroblast cultures. The present study was performed to investigate the in vitro cytotoxic and genotoxic potential effects of D-003 assessed through two tests: the neutral red (NR) assay and the Ames test. Positive and negative controls were included in each experimental series. Compared with controls, no cytotoxicity was evident after 24 and 72 h of treatment with doses up to 1,000 microg/ml in the NR assay. On the other hand, D-003 (5-5,000 microg/plate) did not increase the frequency of reverse mutations in the Ames test in both alternatives with or without S9 mix metabolic activation and a pre-incubation step. The positive control chemicals included in each experiment, namely, treatment with sodium dodecyl sulphate (SDS) in the NR assay and sodium azide (NaAz), 2-aminofluorene (AF), and dimethylnitrosamine (DMNA) in the Ames test, induced the expected changes, such as a decrease in optical density (OD) values in the NR assay and an increase in the frequency of reverse mutations in the Ames test. The present results indicate that D-003 did not show evidence of cytotoxic or genotoxic potential in tests able to detect the ability of chemicals to disrupt cells (NR assay) or to induce gene mutations (Ames test). Copyright 2002 Wiley-Liss, Inc.
机译:D-003是从甘蔗蜡中纯化的很长链脂肪酸的混合物,其中十八烷酸为主要成分。先前的实验研究表明D-003抑制了啮齿动物的血小板聚集。同样,它以剂量依赖性方式降低了常胆固醇血症兔的总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C),并抑制了成纤维细胞培养物中胆固醇的生物合成。进行本研究以研究通过两种测试评估的D-003的体外细胞毒性和遗传毒性潜在影响:中性红(NR)分析和Ames测试。阳性和阴性对照都包括在每个实验系列中。与对照组相比,在NR分析中,剂量高达1,000 microg / ml的药物治疗24和72小时后,没有明显的细胞毒性。另一方面,在有或没有S9混合代谢激活和预孵育步骤的两种选择中,D-003(5-5,000微克/板)在Ames测试中均未增加反向突变的频率。每个实验中包括的阳性对照化学品,即在NR分析中用十二烷基硫酸钠(SDS)处理,在Ames测试中用叠氮化钠(NaAz),2-氨基芴(AF)和二甲基亚硝胺(DMNA)处理,可以达到预期的效果变化,例如NR分析中的光密度(OD)值降低,以及Ames测试中反向突变的频率增加。目前的结果表明,D-003在能够检测化学物质破坏细胞的能力(NR分析)或诱导基因突变的能力(Ames试验)中没有显示出细胞毒性或遗传毒性的证据。版权所有2002 Wiley-Liss,Inc.

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