Impact of oxygen free radicals in rat partial liver transplantation

• Published in: The Journal of surgical research 2014-10, Vol.191 (2), p.469-475
• Main Authors: Srinivasan, Pramod Kadaba, MSc, Yagi, Shintaro, MD, PhD, Nagai, Kazuyuki, MD, PhD, Afify, Mamdouh, VVM, PhD, Hata, Koichiro, MD, PhD, Uemoto, Shinji, MD, PhD, Tolba, Rene H., MD, PhD
• Format: Article
• Language: English
• Subjects: Acetylcysteine - pharmacology; Animals; Free Radicals - metabolism; HTK; Lipid Peroxidation; Liver Transplantation; Male; Microcirculation; N-Acetylcysteine; Organ Preservation; Oxygen - metabolism; Partial liver transplantation; Rats; Rats, Inbred Lew; Surgery; Warm ischemia
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2014.05.002

Abstract Background Due to the shortage of suitable organs, the demand for partial liver transplantation from living donors has increased worldwide. N-acetylcysteine (NAC) has shown protective effects as a free radical scavenger during hypothermic preservation and warm ischemia–reperfusion liver injury; however, no study has reported the effects in partial liver transplantation. The aim of this study was to analyze the impact of NAC on liver graft microcirculation and graft function after partial liver transplantation in rats. Methods Orthotopic partial liver transplantations were performed in 40 rats following cold storage in histidine-tryptophan-ketoglutarate solution for 3 h with 20 mM NAC (NAC group, n  = 20) or without (control group, n  = 20). We assessed portal circulation, graft microcirculation, and biochemical analyses of plasma at 1, 3, 24, and 168 h after portal reperfusion. Results (Control versus NAC, median and range): Portal venous pressure was significantly lower with NAC ( P  = 0.03). Microcirculation measured by laser Doppler was significantly improved with NAC throughout the time course ( P  = 0.003). Alanine aminotransferase levels were significantly lower in the NAC group ( P  < 0.05). Total antioxidative capacity was significantly higher in the NAC group at 1 h after reperfusion (Trolox equivalents: median, 3 μM; range, 2.9–6.7 versus median, 16.45 μM; range, 10.4–18.8). Lipid peroxidation was significantly abrogated in the NAC group (median, 177.6 nmol/mL; range, 75.9–398.1 versus median, 71.5 nmol/mL; range, 58.5–79 at 3 h). Conclusions This study showed that NAC treatment during cold storage resulted in improved microcirculation and preservation quality of partial liver graft likely because of enhanced antioxidant capacity and reduced lipid peroxidation.