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[N-乙酰半胱氨酸在优化特定药物治疗中的应用]

[The application of N-acetylcysteine in optimization of specific pharmacological therapies].

作者信息

Hołyńska-Iwan Iga, Wróblewski Marcin, Olszewska-Słonina Dorota, Tyrakowski Tomasz

机构信息

Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum in Bydgoszcz: Department of Pathobiochemistry and Clinical Chemistr, Faculty of Pharmacy.

Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum in Bydgoszcz: Department of Biochemistry, Faculty of Medicine.

出版信息

Pol Merkur Lekarski. 2017 Sep 29;43(255):140-144.

Abstract

Based on the analysis of data from clinical trials it could be postulated that N-acetylcysteine has a positive impact on the treatment of various diseases. However, less is known about specific molecular and physiological mechanisms underlying the reported therapeutic effects. N-acetylcysteine (NAC, N-acetyl-L-cysteine) is an amino acid derivative containing a thiol group. It is a precursor of L-cysteine and glutathione. NAC is well absorbed and safe for the body at doses up to 300 mg per kg of body weight. Side effects are relatively rare. NAC is used as an mucolytic agent in adjunctive therapy of respiratory diseases causing the retention of secretions, as well as an antidote in the treatment of paracetamol poisoning. Moreover, NAC protects against the toxic effects of reactive oxygen species and their active metabolites. NAC is involved in free radical scavenging processes via several independent mechanisms, including a direct reduction of free radicals, providing substrates for oxidation-reduction reactions and activation of antioxidant enzymes. In the blood, NAC decreases the level of low density lipoprotein peroxidation. In various tissues, NAC may increase the levels of glutathione and cysteine and stimulate the superoxide dismutase action. NAC is used as a supplement in the treatment of various diseases associated with impaired exterior and intracellular oxidative balance. NAC increases the concentrations of amino acids and their derivatives, including cysteine, cystine, and glutathione. It also stabilizes the antioxidant status of the cells and the intercellular spaces. NAC changes the levels of transcription factors, modifying the transcription of selected genes and acting on the protein translation. It works on the activation of several enzymes in the cells and outside the cells. Based on the analysis of data from clinical trials it can be concluded, that an administration of NAC may be beneficial for these groups of patients, in whom the reversible accumulation and the negative action of free radicals was observed.

摘要

基于对临床试验数据的分析,可以推测N - 乙酰半胱氨酸对多种疾病的治疗具有积极影响。然而,对于所报道治疗效果背后的具体分子和生理机制,人们了解得较少。N - 乙酰半胱氨酸(NAC,N - 乙酰 - L - 半胱氨酸)是一种含巯基的氨基酸衍生物。它是L - 半胱氨酸和谷胱甘肽的前体。NAC吸收良好,在体重每千克300毫克的剂量下对身体安全。副作用相对较少。NAC在伴有分泌物潴留的呼吸道疾病辅助治疗中用作黏液溶解剂,以及在对乙酰氨基酚中毒治疗中用作解毒剂。此外,NAC可抵御活性氧及其活性代谢产物的毒性作用。NAC通过多种独立机制参与自由基清除过程,包括直接还原自由基、为氧化还原反应提供底物以及激活抗氧化酶。在血液中,NAC可降低低密度脂蛋白的过氧化水平。在各种组织中,NAC可能会增加谷胱甘肽和半胱氨酸的水平,并刺激超氧化物歧化酶的活性。NAC用作治疗与细胞内外氧化平衡受损相关的各种疾病的补充剂。NAC可增加氨基酸及其衍生物的浓度,包括半胱氨酸、胱氨酸和谷胱甘肽。它还能稳定细胞和细胞间隙的抗氧化状态。NAC会改变转录因子的水平,修饰特定基因的转录并作用于蛋白质翻译。它作用于细胞内和细胞外多种酶的激活。基于对临床试验数据的分析可以得出结论,对于观察到自由基可逆性积累和负面作用的这些患者群体,给予NAC可能有益。

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