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硫转移酶和氰化物解毒在小鼠肝、肾和脑。

Sulfurtransferases and cyanide detoxification in mouse liver, kidney, and brain.

机构信息

Institute of Medical Biochemistry, Department of Biology, Collegium Medicum UJ, 31-034 Kraków, ul. Kopernika 7, Poland.

出版信息

Toxicol Mech Methods. 2004;14(6):331-7. doi: 10.1080/15376520490434683.

Abstract

The activity of rhodanese, 3-mercaptopyruvate sulfurtransferase (MPST) and cystathionase in mouse liver, kidney, and four brain regions: tele-, meso-, di- and rhombencephalon was studied 30 min and 2 h following a sublethal dose of cyanide (4 mg/ kg body weight) intraperitoneal injection. Simultaneously, sulfane sulfur levels and total sulfur content, a direct or indirect source of sulfur for CN(-) conversion to SCN(-), were also investigated in these tissues. In the liver this dose of cyanide seemed to impair the process of cyanide detoxification by MPST, as well as rhodanese inhibition. The effects of cyanide administration to mice proved to be totally different in the liver and kidney. In the kidney, a significant increase in the rhodanese activity was observed as early as 30 min following cyanide intoxication, and an elevated cystathionase activity after 2 h was detected. This suggests the involvement of cystathionase in cyanide detoxification in the kidney. The activity of MPST remained at the same level as in the control group. In the rhombencephalon, similarly as in the kidney, L-cysteine desulfuration pathways, which generate sulfane sulfur and sulfurtransferases that transfer sulfane sulfur atoms to CN(-), seemed to play an important role as a defense system against cyanide. The stable level of sulfane sulfur and total sulfur content was accompanied in the rhombencephalon by an increased activity of MPST, cystathionase and rhodanese. In other brain regions the role of these three sulfurtransferases was not so clear and it seemed that in the telencephalon, where the total sulfur content, but not the sulfane sulfur level, was significantly increased, some sulfur-containing compounds, such as GSH and/or cysteine, appeared in response to cyanide.

摘要

氰化物(4 毫克/千克体重)腹腔注射亚致死剂量 30 分钟和 2 小时后,研究了小鼠肝、肾和四个脑区(端脑、间脑、中脑和后脑)中天冬氨酸转氨甲酰酶、3-巯基丙酮酸硫转移酶(MPST)和胱硫醚酶的活性,同时还研究了这些组织中硫烷硫水平和总硫含量(CN-转化为 SCN-的直接或间接硫源)。在肝脏中,这种剂量的氰化物似乎会损害 MPST 对氰化物解毒的过程,以及对硫代鸟嘌呤酶的抑制作用。氰化物对小鼠的影响在肝脏和肾脏中完全不同。在肾脏中,氰化物中毒后 30 分钟即可观察到硫代鸟嘌呤酶活性显著增加,2 小时后检测到胱硫醚酶活性升高。这表明胱硫醚酶参与了肾脏中的氰化物解毒。MPST 的活性与对照组相同。在后脑,与肾脏类似,生成硫烷硫和将硫烷硫原子转移到 CN-的硫转移酶的 L-半胱氨酸脱硫途径似乎作为防御系统对氰化物发挥了重要作用。在后脑,稳定的硫烷硫和总硫含量伴随着 MPST、胱硫醚酶和硫代鸟嘌呤酶活性的增加。在其他脑区,这三种硫转移酶的作用并不明显,在前脑,总硫含量(而非硫烷硫水平)显著增加,似乎是为了应对氰化物,出现了一些含硫化合物,如 GSH 和/或半胱氨酸。

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