title: Propargylglycine aggravates liver damage in LPS-treated rats: Possible relation of nitrosative stress with the inhibition of H2S formation.
abstract: BACKGROUND
  Hydrogen sulfide (H2S) is a naturally occurring gaseous transmitter, which may play important roles in normal physiology and disease. Here, we investigated the effect of endogenously formed H2S in the endotoxemic organ injury.
  
  
  METHODS
  Male Wistar rats were subjected to acute endotoxemia [Escherichia coli lipopolysaccharide (LPS) 20 mg kg(-1), intraperitoneally (ip)]. A group of animals was injected d,l-propargylglycine (PAG, 50 mg kg(-1), ip), an inhibitor of the H2S-synthesizing enzyme cystathionine-γ-lyase (CSE), 60 min before LPS administration. Six hours after the LPS treatment, animals were sacrificed. Myeloperoxidase (MPO), dimethylarginine dimethylaminohydrolase (DDAH) activities and levels of nitrotyrosine and GSH were measured in the liver. Asymmetric dimethylarginine (ADMA) and arginine levels in both liver and plasma were determined using HPLC.
  
  
  RESULTS
  LPS injections caused liver injury, as evidenced by the activities of serum aspartate aminotransferase and arginase. After LPS injections, increased arginine content and arginine/ADMA ratio were observed in the liver, together with significant decrements in both DDAH activity and GSH levels. Despite the accumulation of ADMA in the plasma, its level remained unchanged in the liver. PAG pretreatment aggravated the LPS-induced increase in the activities of MPO and serum enzymes. The most profound effect of PAG pretreatment was observed in nitrotyrosine levels in the liver, which were increased significantly as compared with the control and LPS-injected groups.
  
  
  CONCLUSIONS
  These findings support the view that the suppression of nitrosative stress by endogenous H2S is one of the mechanisms to protect liver against endotoxemic injury.
authors.affiliation: Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. Electronic address: seldabekpinar@hotmail.com.
authors.forename: Seldag
authors.initials: S
authors.lastname: Bekpinar
authors.affiliation: Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. Electronic address: ymyu@istanbul.edu.tr.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Unlucerci
authors.affiliation: Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. Electronic address: mmujdatuysal@hotmail.com.
authors.forename: Mujdat
authors.initials: M
authors.lastname: Uysal
authors.affiliation: Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. Electronic address: figur@istanbul.edu.tr.
authors.forename: Figen
authors.initials: F
authors.lastname: Gurdol
mesh_terms: D000480:Alkynes / Q000494:pharmacology*; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D019446:Endotoxemia / Q000503:physiopathology*; D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008107:Liver Diseases / Q000503:physiopathology*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000480:Alkynes; D008070:Lipopolysaccharides; C002744:3-nitrotyrosine; D014443:Tyrosine; C018524:N,N-dimethylarginine; C009055:propargylglycine; D001120:Arginine; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000581:Amidohydrolases; C059999:dimethylargininase; D003542:Cystathionine gamma-Lyase; D005978:Glutathione; D005998:Glycine; D006862:Hydrogen Sulfide
keywords: Asymmetric dimethylarginine; Hydrogen sulfide; Lipopolysaccharide; Nitrotyrosine; d,l-Propargylglycine