Many toxic effects of cocaine are attributed to reactive oxygen species (ROS) generated during its metabolism. Recently, it has been suggested that the biological action of ROS is often confused with endogenously generated reactive sulfur species (RSS). The aim of this study was to evaluate the impact of cocaine on thiols and RSS in the rat liver and kidney in the drug self-administration (SA) paradigm and the cocaine yoked delivery model (YC) followed by drug abstinence with extinction training. The level of thiols as well as RSS formed during anaerobic metabolism of cysteine and sulfate were assayed. In addition, the activity of enzymes involved in RSS formation and glutathione metabolism were determined. In the liver, following direct cocaine administration (SA and YC), the RSS levels decreased, while in the kidneys, cocaine increased the RSS contents in both groups. These changes were maintained in these tissues during drug abstinence. The level of sulfates was changed by cocaine only in the liver. In the kidney, cocaine shifted cysteine metabolism towards an anaerobic pathway. Our study demonstrates for the first time the changes in cysteine metabolism and thiol levels in the liver and kidney of rats after cocaine self-administration and abstinence.

中文翻译：

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静脉注射可卡因和禁欲后大鼠肝脏和肾脏中半胱氨酸代谢的评估

可卡因的许多毒性作用归因于其代谢过程中产生的活性氧（ROS）。近来，已经提出ROS的生物作用经常与内生产生的反应性硫物质（RSS）混淆。这项研究的目的是评估可卡因对药物自我给药（SA）范式和可卡因轭铁传递模型（YC）在大鼠禁食和灭绝训练中对大鼠肝脏和肾脏中硫醇和RSS的影响。测定了半胱氨酸和硫酸盐的厌氧代谢过程中形成的硫醇水平以及RSS。此外，确定了参与RSS形成和谷胱甘肽代谢的酶的活性。在肝脏中，直接施用可卡因后（SA和YC），RSS含量下降，而在肾脏中，可卡因增加了两组中的RSS含量。在戒毒期间，这些变化在这些组织中得以维持。仅在肝脏中可卡因改变了硫酸盐的水平。在肾脏中，可卡因将半胱氨酸代谢转移至厌氧途径。我们的研究首次证明了可卡因自我给药和禁欲后大鼠肝脏和肾脏中半胱氨酸代谢和巯基水平的变化。