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柠檬醛和丁香酚可调节小鼠腹腔巨噬细胞中的DNA损伤和促炎介质基因。

Citral and eugenol modulate DNA damage and pro-inflammatory mediator genes in murine peritoneal macrophages.

作者信息

Porto Marilia de Paula, da Silva Glenda Nicioli, Luperini Bruno Cesar Ottoboni, Bachiega Tatiana Fernanda, de Castro Marcondes João Paulo, Sforcin José Maurício, Salvadori Daisy Maria Fávero

机构信息

Departamento de Patologia, Faculdade de Medicina de Botucatu, UNESP - Universidade Estadual Paulista, Botucatu, SP, 18618-000, Brazil,

出版信息

Mol Biol Rep. 2014 Nov;41(11):7043-51. doi: 10.1007/s11033-014-3657-9.

Abstract

Citral and eugenol have been broadly studied because of their anti-inflammatory, antioxidant and antiparasitic potentials. In this study, the effects of citral (25, 50 and 100 µg/mL) and eugenol (0.31, 0.62, 1.24 and 2.48 µg/mL) on the expression (RT-PCR) of the pro-inflammatory mediator genes NF-κB1, COX-2 and TNF-α were evaluated in mouse peritoneal macrophages with or without activation by a bacterial lipopolysaccharide (LPS). Additionally, the genotoxic potentials of two compounds and their capacities to modulate the DNA damage induced by doxorubicin (DXR) were investigated using the comet assay. The data revealed that neither citral nor eugenol changed COX-2, NF-κB1 or TNF-α expression in resting macrophages. However, in LPS-activated cells, citral induced the hypoexpression of COX-2 (100 µg/mL) and TNF-α (50 and 100 µg/mL). Hypoexpression of TNF-α was also detected after cellular exposure to eugenol at the highest concentration (2.48 µg/mL). Both compounds exhibited genotoxic potential (citral at 50 and 100 µg/mL and eugenol at all concentrations) but also showed chemopreventive effects, in various treatment protocols. Both citral and eugenol might modulate inflammatory processes and DXR-induced DNA damage, but the use of these compounds must be viewed with caution because they are also able to induce primary DNA lesions.

摘要

由于柠檬醛和丁香酚具有抗炎、抗氧化和抗寄生虫的潜力,因此它们受到了广泛的研究。在本研究中,评估了柠檬醛(25、50和100µg/mL)和丁香酚(0.31、0.62、1.24和2.48µg/mL)对促炎介质基因NF-κB1、COX-2和TNF-α表达(RT-PCR)的影响,实验对象为有或无细菌脂多糖(LPS)激活的小鼠腹腔巨噬细胞。此外,使用彗星试验研究了这两种化合物的遗传毒性潜力及其调节阿霉素(DXR)诱导的DNA损伤的能力。数据显示,柠檬醛和丁香酚均未改变静息巨噬细胞中COX-2、NF-κB1或TNF-α的表达。然而,在LPS激活的细胞中,柠檬醛诱导了COX-2(100µg/mL)和TNF-α(50和100µg/mL)的低表达。细胞暴露于最高浓度(2.48µg/mL)的丁香酚后,也检测到TNF-α的低表达。两种化合物在各种处理方案中均表现出遗传毒性潜力(柠檬醛在50和100µg/mL,丁香酚在所有浓度),但也显示出化学预防作用。柠檬醛和丁香酚都可能调节炎症过程和DXR诱导的DNA损伤,但使用这些化合物时必须谨慎,因为它们也能够诱导原发性DNA损伤。

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