Attenuation of ischemic injury by N-acetylcysteine preconditioning of the liver.
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.
Smyrniotis
Vassilios
V
Second Department of Surgery, University of Athens School of Medicine, Aretaeion Hospital, Athens, Greece.
Arkadopoulos
Nikolaos
N
Kostopanagiotou
Georgia
G
Theodoropoulos
Theodoros
T
Theodoraki
Kassiani
K
Farantos
Charalampos
C
Kairi
Evi
E
Paphiti
Agathi
A
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
D000242:Cyclic AMP; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000111:Acetylcysteine