The Chair of Medical Biochemistry, Jagiellonian University Medical College, 7, Kopernik Street, 31-034, Kraków, Poland.
Neurotox Res. 2013 Oct;24(3):345-57. doi: 10.1007/s12640-013-9395-2. Epub 2013 Apr 27.
Cyanate is formed mostly during nonenzymatic urea biodegradation. Its active form isocyanate reacts with protein -NH2 and -SH groups, which changes their structure and function. The present studies aimed to investigate the effect of cyanate on activity of the enzymes, which possess -SH groups in the active centers and are implicated in anaerobic cysteine transformation and cyanide detoxification, as well as on glutathione level and peroxidative processes in different brain structures of the rat: cortex, striatum, hippocampus, and substantia nigra. In addition, we examined whether a concomitant treatment with lipoate, a dithiol that may act as a target of S-carbamoylation, can prevent these changes. Cyanate-inhibited sulfurtransferase activities and lowered sulfide level, which was accompanied by a decrease in glutathione concentration and elevation of reactive oxygen species level in almost all rat brain structures. Lipoate administered in combination with cyanate was able to prevent the above-mentioned negative cyanate-induced changes in a majority of the examined brain structures. These observations can be promising for chronic renal failure patients since lipoate can play a double role in these patients contributing to efficient antioxidant defense and protection against cyanate and cyanide toxicity.
氰酸盐主要在非酶促尿素生物降解过程中形成。其活性形式异氰酸酯与蛋白质的 -NH2 和 -SH 基团反应，改变其结构和功能。本研究旨在探讨氰酸盐对具有活性中心 -SH 基团的酶的活性、涉及厌氧半胱氨酸转化和氰化物解毒的酶，以及对不同脑结构（皮质、纹状体、海马和黑质）大鼠谷胱甘肽水平和过氧化物酶过程的影响：皮质、纹状体、海马和黑质。此外，我们还研究了同时用硫辛酸（一种可能作为 S-氨甲酰化靶标的二硫醇）治疗是否可以预防这些变化。氰酸盐抑制了硫转移酶的活性，降低了硫化物水平，这伴随着谷胱甘肽浓度的降低和几乎所有大鼠脑结构中活性氧水平的升高。与氰酸盐联合给予硫辛酸能够预防大多数检查的脑结构中上述氰酸盐引起的负面变化。这些观察结果对慢性肾衰竭患者具有很大的希望，因为硫辛酸在这些患者中可以发挥双重作用，有助于有效的抗氧化防御和对氰酸盐和氰化物毒性的保护。
