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. AIMS: 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 687-694 |
| Number of pages | 8 |
| Journal | Transplantation |
| Volume | 94 |
| Issue number | 7 |
| DOIs | |
| State | Published - Oct 15 2012 |
Fingerprint
Keywords
- Living-donor liver transplantation
- Oxidant stress
- Small-for-size syndrome
- SOD mimetics
ASJC Scopus subject areas
- Transplantation
Cite this
SOD mimetic improves the function, growth, and survival of small-size liver grafts after transplantation in rats. / Cui, Yi Yao; Qian, Jian Min; Yao, Ai Hua; Ma, Zhen Yu; Qian, Xiao Feng; Zha, Xiao Min; Zhao, Yi; Ding, Qiang; Zhao, Jia; Wang, Shui; Wu, Jian.
In: Transplantation, Vol. 94, No. 7, 15.10.2012, p. 687-694.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SOD mimetic improves the function, growth, and survival of small-size liver grafts after transplantation in rats
AU - Cui, Yi Yao
AU - Qian, Jian Min
AU - Yao, Ai Hua
AU - Ma, Zhen Yu
AU - Qian, Xiao Feng
AU - Zha, Xiao Min
AU - Zhao, Yi
AU - Ding, Qiang
AU - Zhao, Jia
AU - Wang, Shui
AU - Wu, Jian
PY - 2012/10/15
Y1 - 2012/10/15
N2 - 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. AIMS: 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.
AB - 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. AIMS: 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.
KW - Living-donor liver transplantation
KW - Oxidant stress
KW - Small-for-size syndrome
KW - SOD mimetics
UR - http://www.scopus.com/inward/record.url?scp=84867240168&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867240168&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e3182633478
DO - 10.1097/TP.0b013e3182633478
M3 - Article
VL - 94
SP - 687
EP - 694
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 7
ER -