Wróbel Maria, Góralska Joanna, Jurkowska Halina, Sura Piotr
Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7, 31-034 Kraków, Poland.
Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7, 31-034 Kraków, Poland.
Biochimie. 2017 Apr;135:181-185. doi: 10.1016/j.biochi.2017.02.006. Epub 2017 Feb 21.
The aim of the present study was to analyze the relative antioxidant effects of acetylsalicylic acid (ASA) and sodium nitroprusside (SNP) in mouse liver and brain.
The activity of rhodanese, 3-mercaptopyruvate sulfurtransferase (MPST) and γ-cystathionase (CSE), functioning as antioxidant proteins and capable of producing HS, was investigated in mouse liver and brain after intraperitoneal once a day administration of sodium nitroprusside (5 mg/kg body weight) or acetylsalicylic acid (500 mg/kg body weight) continued for 5 days. The tissues were homogenized and then the obtained supernatants were used for further determinations. At the same time, the levels of sulfane sulfur, reduced and oxidized glutathione, cysteine, cystine, and cystathionine were also studied in these tissues.
Both ASA and SNP show a statistically significant increase of sulfurtransferases activities in liver. The mechanism of action of sodium nitroprusside appears to consist in liberation of nitric oxide (NO), an important signaling molecule in the mammalian body. SNP also releases cyanide ions, which are converted in the liver to thiocyanate by the enzyme rhodanese and/or MPST and/or γ-cystathionase - the activities of all the enzymes were elevated in reaction to SNP. The action of γ-cystathionase is dependent upon converting cystathionine to cysteine, a precursor of the major cellular antioxidant, glutathione. Under oxidizing conditions, an increase in cystathionine β-synthase activity might indirectly result in an increase in the antioxidant glutathione level; this was reflected by the increased GSH/GSSG ratio in the liver, but not in the brain, where a trace activity of γ-cystathionase is normally detected.
The results of the present investigations show that ASA and SNP may stimulate the GSH-dependent antioxidant system and protect liver cells from oxidative stress. An increased activity of the HS-producing enzymes and the increased GSH/GSSG ratio may lead to an elevated level of HS, a molecule with antioxidant properties. A similar effect was not observed in the brain. In case of both sodium nitroprusside and aspirin administration, homeostasis of sulfane sulfur level was noted in both the liver and brain.
本研究的目的是分析乙酰水杨酸(ASA)和硝普钠(SNP)对小鼠肝脏和大脑的相对抗氧化作用。
每天腹腔注射硝普钠(5毫克/千克体重)或乙酰水杨酸(500毫克/千克体重),持续5天,之后检测小鼠肝脏和大脑中作为抗氧化蛋白且能够产生硫化氢(HS)的硫氰酸酶、3-巯基丙酮酸硫转移酶(MPST)和γ-胱硫醚酶(CSE)的活性。将组织匀浆,然后将获得的上清液用于进一步检测。同时,还研究了这些组织中硫烷硫、还原型和氧化型谷胱甘肽、半胱氨酸、胱氨酸和胱硫醚的水平。
ASA和SNP均使肝脏中硫转移酶的活性有统计学意义的增加。硝普钠的作用机制似乎在于释放一氧化氮(NO),这是哺乳动物体内一种重要的信号分子。SNP还会释放氰离子,氰离子在肝脏中被硫氰酸酶和/或MPST和/或γ-胱硫醚酶转化为硫氰酸盐——所有这些酶的活性在对SNP的反应中均升高。γ-胱硫醚酶的作用取决于将胱硫醚转化为半胱氨酸,半胱氨酸是主要细胞抗氧化剂谷胱甘肽的前体。在氧化条件下,胱硫醚β-合酶活性的增加可能间接导致抗氧化剂谷胱甘肽水平的增加;这在肝脏中表现为GSH/GSSG比值升高,但在大脑中未观察到,大脑中通常检测到γ-胱硫醚酶的微量活性。
本研究结果表明,ASA和SNP可能刺激依赖谷胱甘肽的抗氧化系统,并保护肝细胞免受氧化应激。产生HS的酶活性增加以及GSH/GSSG比值升高可能导致具有抗氧化特性的分子HS水平升高。在大脑中未观察到类似效果。在给予硝普钠和阿司匹林的情况下,肝脏和大脑中均观察到硫烷硫水平的稳态。