title: Attenuation of ischemic injury by N-acetylcysteine preconditioning of the liver.
abstract: BACKGROUND
  Numerous previous studies have established the hepatoprotective properties of N-acetylcysteine (NAC). The present study was designed to investigate the effects of NAC on a warm hepatic ischemia-reperfusion rat model with a focus on the role of cAMP.
  
  
  METHODS
  Fifty-six male Wistar rats were allocated randomly into the control group (n = 28) or the study group (group NAC, n = 28). Group NAC animals received an intravenous bolus dose of 0.3 mg/g NAC, whereas control animals were given an equal volume of normal saline. Subsequently, 60-min partial liver ischemia was induced by occlusion of blood inflow to the left and middle liver lobes. Aspartate aminotransferase, alanine aminotransferase, and alpha-glutathione S-transferase levels, platelet aggregation, and ischemic tissue cyclic adenosine 5-monophosphate (cAMP) levels were examined at 30, 60, and 120 min after reperfusion. Parts of the ischemic liver were sampled at the same time-points. Measurements were obtained from seven animals at each time point.
  
  
  RESULTS
  The administration of NAC resulted in lower levels of aspartate aminotransferase, alanine aminotransferase, and alpha-glutathione S-transferase, decreased platelet aggregation, and increased levels of ischemic tissue cAMP at all time points after reperfusion. Histologically, fewer necrotic changes were observed in the NAC group at 60 and 120 min after reperfusion. All differences were statistically significant (P < 0.05).
  
  
  CONCLUSIONS
  In the present study, NAC seems to attenuate hepatic ischemia-reperfusion damage, as demonstrated by liver function tests and liver histology. The effects of NAC appear to be mediated by the decrease in platelet aggregation and increase in the levels of cAMP observed in ischemic liver tissue.
authors.affiliation: Second Department of Surgery, University of Athens School of Medicine, Aretaeion Hospital, Athens, Greece.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Smyrniotis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Arkadopoulos
authors.forename: Georgia
authors.initials: G
authors.lastname: Kostopanagiotou
authors.forename: Theodoros
authors.initials: T
authors.lastname: Theodoropoulos
authors.forename: Kassiani
authors.initials: K
authors.lastname: Theodoraki
authors.forename: Charalampos
authors.initials: C
authors.lastname: Farantos
authors.forename: Evi
authors.initials: E
authors.lastname: Kairi
authors.forename: Agathi
authors.initials: A
authors.lastname: Paphiti
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D000242:Cyclic AMP / Q000378:metabolism; D005982:Glutathione Transferase / Q000097:blood; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D000242:Cyclic AMP; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000111:Acetylcysteine