Kowalczyk-Pachel Danuta, Iciek Małgorzata, Bilska-Wilkosz Anna, Górny Magdalena, Jastrzębska Joanna, Kamińska Kinga, Dudzik Paulina, Filip Małgorzata, Lorenc-Koci Elżbieta
The Chair of Medical Biochemistry, Medical College, Jagiellonian University, 7, Kopernika St., PL-31-034 Kraków, Poland.
Maj Institute of Pharmacology, Polish Academy of Sciences, 12, Smętna St., PL-31-343 Kraków, Poland.
Antioxidants (Basel). 2021 Jan 8;10(1):74. doi: 10.3390/antiox10010074.
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.
可卡因的许多毒性作用都归因于其代谢过程中产生的活性氧（ROS）。最近，有人提出ROS的生物学作用常常与内源性产生的活性硫物种（RSS）相混淆。本研究的目的是评估在药物自我给药（SA）范式和可卡因配对给药模型（YC）中，可卡因对大鼠肝脏和肾脏中硫醇和RSS的影响，随后通过消退训练进行药物戒断。测定了半胱氨酸和硫酸盐厌氧代谢过程中形成的硫醇以及RSS的水平。此外，还测定了参与RSS形成和谷胱甘肽代谢的酶的活性。在肝脏中，直接给予可卡因（SA和YC）后，RSS水平降低，而在肾脏中，两组的可卡因均增加了RSS含量。在药物戒断期间，这些组织中的这些变化得以维持。硫酸盐水平仅在肝脏中因可卡因而改变。在肾脏中，可卡因使半胱氨酸代谢转向厌氧途径。我们的研究首次证明了可卡因自我给药和戒断后大鼠肝脏和肾脏中半胱氨酸代谢和硫醇水平的变化。
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