N-acetylcysteine ameliorates liver injury in a rat model of intestinal ischemia reperfusion

J Surg Res. 2016 Dec;206(2):263-272. doi: 10.1016/j.jss.2016.08.049. Epub 2016 Aug 19.

Abstract

Background: N-acetylcysteine (NAC) is an antioxidant with direct and indirect antioxidant actions used in the clinical setting. Oxidative stress is known to play a pivotal role in the intestinal ischemia reperfusion (IIR). Therefore, we studied the effect of different pretreatment regimens with NAC on the IIR injury in rats.

Materials and methods: Thirty-five male Wistar rats were randomly assigned to five groups. In group sham, only laparotomy was performed. Group control underwent IIR without NAC. In the other groups, NAC was administered intraperitoneally with different regimens: 150 mg/kg before ischemia (NAC 150), 300 mg/kg before ischemia (NAC 300), and 150 mg/kg before ischemia plus 150 mg/kg 5 min before reperfusion (NAC 150 + 150). Measurements in tissues and blood were conducted at 4 h of reperfusion following exsanguination.

Results: Histological score of the liver was significantly improved in NAC 300 compared with control (1.7 ± 0.5 versus 2.9 ± 1.1, respectively, P = 0.05). In addition, NAC treatment significantly reduced liver transaminases in all groups of treatment, mostly in group NAC 300. Plasma malondialdehyde levels were lower with NAC treatment, although not statistically significant. Lung glutathione peroxidase was significantly increased in group NAC 300 (P = 0.04), while the other oxidation biomarkers showed no significant differences.

Conclusions: NAC exerts a significant protective role in liver injury following IIR, which seems to be independent of an intestinal protective effect. Additional administration of NAC before reperfusion was of no further benefit. The most effective regimen among the compared regimens was that of 300 mg/kg before ischemia.

Keywords: Intestinal ischemia reperfusion; Liver injury; N-acetylcysteine; Oxidative stress; Rat model.

MeSH terms

  • Acetylcysteine / pharmacology
  • Acetylcysteine / therapeutic use*
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Biomarkers / metabolism
  • Hepatic Insufficiency / etiology
  • Hepatic Insufficiency / metabolism
  • Hepatic Insufficiency / pathology
  • Hepatic Insufficiency / prevention & control*
  • Injections, Intraperitoneal
  • Intestines / blood supply*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Function Tests
  • Male
  • Oxidative Stress / drug effects
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology

Substances

  • Antioxidants
  • Biomarkers
  • Acetylcysteine