title: SOD mimetic improves the function, growth, and survival of small-size liver grafts after transplantation in rats.
abstract: BACKGROUND
  Small-for-size syndrome (SFSS) may occur when graft volume is less than 45% of the standard liver volume, and it manifests as retarded growth and failure of the grafts and more mortality. However, its pathogenesis is poorly understood, and few effective interventions have been attempted.
  
  
  OBJECTIVE
  The present study aimed to delineate the critical role of oxidant stress in SFSS and protective effects of a superoxide dismutase mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), on graft function, growth, and survival in the recipient rats.
  
  
  METHODS
  Small size graft liver transplantation (SSGLT) was performed to determine the survival, graft injury, and growth. MnTBAP was administered in SSGLT recipients (SSGLT+MnTBAP).
  
  
  RESULTS
  Serum alanine aminotransferase levels were sustained higher in SSGLT recipients, which were correlated with an increased apoptotic cell count and hepatocellular necrosis in liver sections. Malondialdehyde content, gene expression of tumor necrosis factor α and interleukin 1β, and DNA binding activity of nuclear factor-κB in the grafts were increased significantly in SSGLT recipients compared with sham-operated controls. Both phosphorylated p38 mitogen-activated protein kinase and nuclear c-Jun were increased in SSGLT. All these changes were strikingly reversed by the administration of MnTBAP, with an increase in serum superoxide dismutase activity. Moreover, in situ bromodeoxyuridine incorporation demonstrated that graft regeneration was much more profound in the SSGLT+MnTBAP group than in the SSGLT group. Finally, the survival of recipients with MnTBAP treatments was significantly improved.
  
  
  CONCLUSIONS
  Enhanced oxidant stress with activation of the p38/c-Jun/nuclear factor-κB signaling pathway contributes to SFSS-associated graft failure, retarded graft growth, and poor survival. MnTBAP effectively reversed the pathologic changes in SFSS-associated graft failure.
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yi-Yao
authors.initials: YY
authors.lastname: Cui
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Qian
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Yao
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Ma
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Qian
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Zha
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Jia
authors.initials: J
authors.lastname: Zhao
authors.forename: Shui
authors.initials: S
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D001665:Binding Sites; D015415:Biomarkers / Q000097:blood; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology*; D018716:Molecular Mimicry; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D011183:Postoperative Complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D053583:Interleukin-1beta; D008665:Metalloporphyrins; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D014409:Tumor Necrosis Factor-alpha; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D008315:Malondialdehyde; D004247:DNA; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D048051:p38 Mitogen-Activated Protein Kinases