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橙花醇的体内遗传毒性评估。

In vivo genotoxicity assessment of nerolidol.

机构信息

Universidade Estadual Paulista, UNESP, Faculdade de Filosofia e Ciências, Departamento de Fonoaudiologia, Marília, SP 17525-900, Brazil.

出版信息

J Appl Toxicol. 2011 Oct;31(7):633-9. doi: 10.1002/jat.1607. Epub 2010 Nov 19.

DOI:10.1002/jat.1607
PMID:21089164
Abstract

Nerolidol is a sesquiterpenoid component of essential oil used as a flavor and aroma enhancer. It has also been studied as a topical skin penetration enhancer, and has inhibitory activities against S. aureus and E. coli, among other activities. The objective of this study was to evaluate the ability of a single nerolidol treatment to induce DNA damage in peripheral blood and liver cells of mice and micronuclei in polychromatic erythrocytes of bone marrow cells of the same animals. In the dose range-finding assays, the maximum tolerated dose was higher than 2000 mg kg(-1) . The doses used in the experiments were 250, 500 and 2000 mg kg(-1) , administered by gavage in a single dose. Peripheral blood cells were collected 4 and 24 h after the treatments and liver cells 24 h after. At least 100 nucleoids per cell type/animal were analyzed to determine the DNA damage scores and 2000 PCEs per animal for micronuclei in PCEs. The positive control was N-nitroso-N-ethylurea 50 mg kg(-1) . Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE:NCE ratio). The results showed that nerolidol induced weak levels of dose-related DNA damage in both types of cells analyzed, and enhanced the average number of micronucleated cells in the two high doses tested. The PCE:NCE ratio showed no cytotoxicity for the three doses of the compound. The data obtained support the view that nerolidol induces clastogenicity and very weak genotoxicity in the mouse cells tested.

摘要

橙花叔醇是一种倍半萜烯类化合物,存在于精油中,可用作风味增强剂和香气增强剂。它也被研究作为一种局部皮肤渗透增强剂,具有抑制金黄色葡萄球菌和大肠杆菌等活性。本研究的目的是评估单次橙花叔醇处理诱导小鼠外周血和肝细胞 DNA 损伤以及同一动物骨髓细胞多染红细胞微核的能力。在剂量探索试验中,最大耐受剂量高于 2000mg/kg。实验中使用的剂量为 250、500 和 2000mg/kg,单次灌胃给药。处理后 4 和 24 小时采集外周血细胞,24 小时后采集肝细胞。对每种细胞类型/动物至少分析 100 个核来确定 DNA 损伤评分,对每个动物分析 2000 个多染红细胞中的微核。阳性对照物为 N-亚硝基-N-乙基脲 50mg/kg。通过对 200 个连续的总多染性(PCE)和正常染色性(NCE)红细胞(PCE:NCE 比值)进行评分来评估细胞毒性。结果表明,橙花叔醇在两种分析的细胞类型中均诱导出与剂量相关的弱水平 DNA 损伤,并在两种测试的高剂量下增强了微核细胞的平均数量。该化合物的三种剂量均未显示出 PCE:NCE 比值的细胞毒性。所得数据支持橙花叔醇在测试的小鼠细胞中诱导断裂剂和非常弱的遗传毒性的观点。

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