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N-乙酰半胱氨酸、氧代噻唑烷羧酸盐、对乙酰氨基酚及其组合对人皮肤成纤维细胞系(HF2FF)硫芥细胞毒性的保护作用。

The protective effects of N-Acetl-cysteine, oxo-thiazolidine-carboxylate, acetaminophen and their combinations against sulfur mustard cytotoxicity on human skin fibroblast cell line (HF2FF).

作者信息

Saberi Mehdi, Zaree Mahmodabady Ali

机构信息

Dept. of Pharmacology and Toxicology, Chemical Injury Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Dept. of Biochemistry, Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

出版信息

Iran Biomed J. 2009 Oct;13(4):215-21.

Abstract

BACKGROUND

Using human skin-fibroblast cell line HF2FF, the efficacy of some drugs was evaluated against sulfur mustard (SM) cytotoxicity. The drugs were the sulfhydryl containing molecule including N-acetylcysteine (NAC), 2-oxo-thiazolidine-4-carboxylate (OTC) and acetaminophen as glutathione (GSH) stimulator pathway.

METHODS

The protective effects of NAC (0.1 mM), OTC (1.8 mM), and acetaminophen (25 mM) alone or in combination with each other were evaluated on SM (180 M)-induced cytotoxicity. NAC and OTC were applied with SM simultaneously and acetaminophen 30 min before SM exposure, incubated for 1 h and then were rinsed and incubated with fresh medium. The efficacy was evaluated by determination of cells viability, intracellular GSH level and catalase activity 1 and 24 h post SM exposure or co-treatments.

RESULTS

The cells viability was decreased 21.8% and 55.2%, respectively for 1 and 24 h post SM (1 h exposure) incubation. So, the 1-h SM exposure and 24-h treatment incubation were selected for evaluation. While, NAC alone treatment increased the cells viability (25%), GSH level (320%) and catalase activity (18%), the most effective combination was NAC plus OTC and acetaminophen which increased more significantly the cells viability (about 40%), GSH level (470%) and catalase activity (100%).

CONCLUSION

The most effective combination was NAC (0.1 mM) plus OTC (1.8 mM) and acetaminophen (25 mM) which should be used before or concomitant with SM exposure. These drugs may reduce SM toxicity possibly by increment of GSH level and catalase activity. This efficacy needs to be confirmed by in vivo study.

摘要

背景

使用人皮肤成纤维细胞系HF2FF,评估了某些药物对硫芥(SM)细胞毒性的疗效。这些药物是含巯基分子,包括N - 乙酰半胱氨酸(NAC)、2 - 氧代 - 噻唑烷 - 4 - 羧酸(OTC)和作为谷胱甘肽(GSH)刺激途径的对乙酰氨基酚。

方法

评估了NAC(0.1 mM)、OTC(1.8 mM)和对乙酰氨基酚(25 mM)单独或相互组合对SM(180 μM)诱导的细胞毒性的保护作用。NAC和OTC与SM同时应用,对乙酰氨基酚在SM暴露前30分钟应用,孵育1小时,然后冲洗并用新鲜培养基孵育。通过在SM暴露或联合处理后1小时和24小时测定细胞活力、细胞内GSH水平和过氧化氢酶活性来评估疗效。

结果

在SM(1小时暴露)孵育后1小时和24小时,细胞活力分别下降了21.8%和55.2%。因此,选择1小时的SM暴露和24小时的处理孵育进行评估。虽然,单独使用NAC处理可提高细胞活力(25%)、GSH水平(320%)和过氧化氢酶活性(18%),但最有效的组合是NAC加OTC和对乙酰氨基酚,其更显著地提高了细胞活力(约40%)、GSH水平(470%)和过氧化氢酶活性(100%)。

结论

最有效的组合是NAC(0.1 mM)加OTC(1.8 mM)和对乙酰氨基酚(25 mM),应在SM暴露之前或同时使用。这些药物可能通过增加GSH水平和过氧化氢酶活性来降低SM毒性。这种疗效需要通过体内研究来证实。

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