Protective effects of N-acetylcysteine on hypothermic ischemia-reperfusion injury of rat liver

Abstract

We investigated whether intraportal injection of 150 mg/kg N-acetylcysteine (NAC) into rats reduced hepatic ischemia-reperfusion injury after 48 hours of cold storage and 2 hours of reperfusion. The organ was isolated and perfused to evaluate liver function. The control group received an intraportal injection of 5% dextrose. NAC increased L-cysteine concentrations 15 minutes after injection (1.29 +/- 0.11 mumol/g vs. 2.68 +/- 0.4 mumol/g, P < .05). However, neither treatment modified glutathione liver concentrations relative to preinjection values. After 48 hours of cold storage and 2 hours of reperfusion, livers from NAC-treated rats produced larger amounts of bile than those in the control group (5.04 +/- 1.92 vs. 0.72 +/- 0.37 microL/g liver; P < .05), and showed a significant reduction in liver injury, as indicated by reduced release of lactate dehydrogenase (679.4 +/- 174.4 vs. 1891.3 +/- 268.3 IU/L/g; P < .01), aspartate transaminase (AST) (13.94 +/- 3.5 vs. 38.75 IU/L/g; P < .01), alanine transaminase ALT) (14.92 +/- 4.09 vs. 45.91 +/- 10.58 IU/L/g; P < .05), and acid phosphatase, a marker of Kupffer cell injury (344.4 +/- 89.6 vs. 927.3 +/- 150.8 IU/L/g; P < .01) in the perfusate. Reduced glutathione concentrations in the perfusate were similar in the two groups (805 +/- 69 vs. 798 +/- 252 nmol/L/g), whereas oxidized glutathione (GSSG) concentrations were higher in the control group (967 +/- 137 vs. 525 +/- 126 nmol/L/g; P < .05). Reduced glutathione (GSH) concentrations in liver tissue collected at the end of perfusion were significantly higher in the NAC group (7.3 +/- 0.9 vs. 4.1 +/- 1.0 mumol/g; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation?

“…Treated livers produced greater amounts of bile and had lower levels of enzymes when compared with controls. 3 Nakano et al 4 reported a direct protective effect on Kupffer cells and an enhancement of the concentration of cysteine within hepatocytes after an intraportal injection of NAC before liver harvesting in rats. Pretreatment with NAC helped maintain hepatic glutathione levels during warm ischemia, whereas when administered after ischemia and before reperfusion, NAC was effective in replenishing depleted glutathione stores in pigs.…”

Effects of Trolox on the activity and gene expression of cytochrome P450 in hepatic ischemia/reperfusion

“…It has been shown that the levels of lipid peroxidation products are lowered when GSH is added to organ storage fluids (Bryan et al, 1994). GSH plays an important role as a free radical scavenger (Nakano et al, 1995). In ischemic rats, hepatic GSH significantly decreased 5 and 24 h after reperfusion.…”

N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation

“…In rat liver transplantation, NAC treatment reduced early phase reperfusion injury [5] and decreased leucocyte adherence to sinusoidal endothelium [23]. In a model of hypothermic I/R injury of the steatotic rat liver, NAC given before cold storage for 24 h diminished sinusoidal microcirculatory injury and lowered enzyme release after reperfusion [24].…”

“…The radical scavenging properties of N-acetylcysteine have been proven beneficial in several conditions involving oxidative damage, namely ischaemia/reperfusion injury in rat liver transplantation [5]. Consequently, NAC has been evaluated as a hepatoprotective agent in clinical OLT and has shown favourable results in a recent study [6], whereas other studies did not demonstrate clinical benefit [7,8].…”