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N-乙酰半胱氨酸和姜黄素对农药诱导的人外周血单个核细胞氧化 DNA 损伤的改善作用。

Ameliorating effect of N-acetylcysteine and curcumin on pesticide-induced oxidative DNA damage in human peripheral blood mononuclear cells.

机构信息

Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi, 110 095, India.

出版信息

Environ Monit Assess. 2011 Aug;179(1-4):293-9. doi: 10.1007/s10661-010-1736-5. Epub 2010 Nov 4.

Abstract

Endosulfan, malathion, and phosphamidon are widely used pesticides. Subchronic exposure to these contaminants commonly affects the central nervous system, immune, gastrointestinal, renal, and reproductive system. There effects have been attributed to increased oxidative stress. This study was conducted to examine the role of oxidative stress in genotoxicity following pesticide exposure using peripheral blood mononuclear cells (PBMC) in vitro. Further possible attenuation of genotoxicity was studied using N-acetylcysteine (NAC) and curcumin as known modulators of oxidative stress. Cultured mononuclear cells was isolated from peripheral blood of healthy volunteers, and exposed to varying concentrations of different pesticides: endosulfan, malathion, and phosphamidon for 6, 12, and 24 h. Lipid peroxidation was assessed by cellular malondialdehyde (MDA) level and DNA damage was quantified by measuring 8-hydroxy-2'-deoxyguanosine (8-OH-dG) using ELISA. Both MDA and 8-OH-dG were significantly increased in a dose-dependent manner following treatment with these pesticides. There was a significant decrease in MDA and 8-OH-dG levels in PBMC when co-treated with NAC or/and curcumin as compared to pesticide alone. These results indicate that pesticide-induced oxidative stress is probably responsible for the DNA damage, and NAC or curcumin attenuate this effect by counteracting the oxidative stress.

摘要

硫丹、马拉硫磷和磷胺是广泛使用的农药。亚慢性接触这些污染物通常会影响中枢神经系统、免疫系统、胃肠道、肾脏和生殖系统。这些影响归因于氧化应激增加。本研究旨在使用体外外周血单核细胞 (PBMC) 研究氧化应激在农药暴露后的遗传毒性中的作用。使用 N-乙酰半胱氨酸 (NAC) 和姜黄素作为氧化应激的已知调节剂,进一步研究了遗传毒性的可能衰减作用。从健康志愿者的外周血中分离出单核细胞进行培养,并将其暴露于不同浓度的不同农药中:硫丹、马拉硫磷和磷胺,分别处理 6、12 和 24 小时。通过细胞丙二醛 (MDA) 水平评估脂质过氧化,通过 ELISA 测量 8-羟基-2'-脱氧鸟苷 (8-OH-dG) 来定量 DNA 损伤。这些农药处理后,MDA 和 8-OH-dG 均呈剂量依赖性显著增加。与单独使用农药相比,当与 NAC 或/和姜黄素共同处理时,PBMC 中的 MDA 和 8-OH-dG 水平显著降低。这些结果表明,农药诱导的氧化应激可能是 DNA 损伤的原因,而 NAC 或姜黄素通过抵消氧化应激来减弱这种作用。

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