title: Cysteine Metabolism and Oxidative Processes in the Rat Liver and Kidney after Acute and Repeated Cocaine Treatment.
abstract: The role of cocaine in modulating the metabolism of sulfur-containing compounds in the peripheral tissues is poorly understood. In the present study we addressed the question about the effects of acute and repeated (5 days) cocaine (10 mg/kg i.p.) administration on the total cysteine (Cys) metabolism and on the oxidative processes in the rat liver and kidney. The whole pool of sulfane sulfur, its bound fraction and hydrogen sulfide (H2S) were considered as markers of anaerobic Cys metabolism while the sulfate as a measure of its aerobic metabolism. The total-, non-protein- and protein- SH group levels were assayed as indicators of the redox status of thiols. Additionally, the activities of enzymes involved in H2S formation (cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3-MST) and GSH metabolism (γ-glutamyl transpeptidase, γ-GT; glutathione S-transferase, GST) were determined. Finally, we assayed the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) as markers of oxidative stress and lipid peroxidation, respectively. In the liver, acute cocaine treatment, did not change concentrations of the whole pool of sulfane sulfur, its bound fraction, H2S or sulfate but markedly decreased levels of non-protein SH groups (NPSH), ROS and GST activity while γ-GT was unaffected. In the kidney, acute cocaine significantly increased concentration of the whole pool of sulfane sulfur, reduced the content of its bound fraction but H2S, sulfate and NPSH levels were unchanged while ROS and activities of GST and γ-GT were reduced. Acute cocaine enhanced activity of the CSE and 3-MST in the liver and kidney, respectively. Repeatedly administered cocaine enhanced the whole pool of sulfane sulfur and reduced H2S level simultaneously increasing sulfate content both in the liver and kidney. After repeated cocaine, a significant decrease in ROS was still observed in the liver while in the kidney, despite unchanged ROS content, a marked increase in MDA level was visible. The repeated cocaine decreased 3-MST and increased γ-GT activities in both organs but reduced GST in the kidney. Our results show that cocaine administered at a relatively low dose shifts Cys metabolism towards the formation of sulfane sulfur compounds which possess antioxidant and redox regulatory properties and are a source of H2S which can support mitochondrial bioenergetics.
authors.affiliation: The Chair of Medical Biochemistry, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Kowalczyk-Pachel
authors.affiliation: The Chair of Medical Biochemistry, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Iciek
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Wydra
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Nowak
authors.affiliation: The Chair of Medical Biochemistry, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Górny
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
authors.affiliation: The Chair of Medical Biochemistry, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Włodek
authors.affiliation: Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Lorenc-Koci
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003542:Cystathionine gamma-Lyase / Q000032:analysis; D003545:Cysteine / Q000378:metabolism*; D005982:Glutathione Transferase / Q000032:analysis; D006706:Homeostasis / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism; D013466:Sulfurtransferases / Q000032:analysis; D005723:gamma-Glutamyltransferase / Q000032:analysis
chemical_list: D017382:Reactive Oxygen Species; D013455:Sulfur; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D003542:Cystathionine gamma-Lyase; D003042:Cocaine; D003545:Cysteine; D006862:Hydrogen Sulfide