Protective effects of N-acetylcysteine against hypothermic ischemia-reperfusion injury to rat liver
- VernacularTitle:N-乙酰半胱氨酸对鼠肝冷缺血/再灌注损伤的保护作用
- Author:
Quan LI
;
Weifeng YU
- Publication Type:Journal Article
- Keywords:
Acetylcysteine;
Liver;
Reperfusion injury;
Hypothermia
- From:
Chinese Journal of Anesthesiology
1994;0(01):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective In order to improve the survival of graft liver after liver transplantation, this study was designed to investigate whether intraportal injection of 150mg/kg N-acetylcysteine (NAC) in rats could reduce hepatic ischemia-reperfusion injury after 48 h of cold storage and 2 h of reperfusion.Methods Healthy male Wistar rats weighing 250-350g were used.The study consisted of three groups: control group (group Ⅰ);NAC-treated group(group Ⅱ).1 ml of 5% dextrose (D5%) or 1 ml D5% containing 150mg/kg NAC was injected into the superior mesenteric vein.15 min after the injection of D5% or NAC the liver was flushed with cold (4℃) Ringer's solution through the portal vein .After perfusion, the liver was removed and kept in 100 ml UW solution at 4℃ for 48 h.In group Ⅲ animals were pretreated with buthionine sulfoximine (BSO) 2 h before intraportal injection of D5% or NAC and liver harvesting.After cold storage, the livers were then perfused for 2 h by a closed circulating system.Aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) activities in the perfusate were determined by reflectometry.Lactate and acid phosphatase activities were determined by enzymatic methods.Results After 48 h of cold storage and 2 h of reperfusion, livers from NAC-treated group produced larger amounts of bile than those in the control group, and released less LDH, AST, ALT and acid phosphatase, a marker of Kupffer cell injury in the perfusate.The protective effects of NAC against cold ischemia-reperfusion liver injury were maintained when animals were pretreated with BSO, a specific inhibitor of glutathione synthesis.Conclusions This study shows that intraportal administration of NAC in vivo significantly improves the initial function of the isolated rat liver.Our results also indicate that NAC inhibits the activation of Kupffer cells, which are the first source of reactive oxygen intermediates during reperfusion.
