N-acetyl cysteine improves glycogenesis after segmental liver ischemia and reperfusion injury in pigs

Abstract

Objective. N-acetylcysteine (NAC) is an antioxidative molecule known to protect liver tissue from oxygen radical species generated during ischemia and reperfusion (IR). Nutritional and toxicology studies have shown that NAC also improves glucose metabolism and glycogen stores. We hypothesized that NAC improves glycogenesis and that impaired glycogenesis is a key element in IR injury. Material and Methods. In an experimental model, 80 min of segmental liver ischemia was induced in 16 pigs and the reperfusion was followed for 360 min. Eight animals received NAC 150 mg/kg as a bolus injection followed by an infusion of NAC 50 mg/kg/h intravenously. Results. AST and leukocyte density were lower in the NAC-treated animals, unrelated to the glutathione levels or apoptosis. Glycogen stores returned to a higher degree in the NAC-treated animals and microdialysis revealed lower levels of lactate during the reperfusion phase. Nitrite/Nitrate levels in the NAC group were lower in both serum and microdialysates, indicating that NAC scavenges radical nitrosative species. Conclusions. NAC treatment improves glycogenesis after liver IR injury and reduces the level of intraparenchymal lactate during reperfusion, possibly due to the scavenging of radical nitrosative species.

Key Words::

• ATP
• glycogen
• hepatobiliary-basic
• ischemia
• liver
• pig
• reperfusion
• surgery

Acknowledgements

The authors thank FORSS, Research council in the southeast region of Sweden and the Bengt Ihre Foundation, through the Swedish Society of Medicine for supporting the research and thank Thomas Karlsson, Sara Gregeborg and Dan Linghammar for their assistance in the animal laboratory. Previous communications: Parts of results presented at the EHPBA meeting in Athens 2009 and at the Swedish surgical week 2009.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.