SOD mimetic improves the function, growth, and survival of small-size liver grafts after transplantation in rats

Yi Yao Cui, Jian Min Qian, Ai Hua Yao, Zhen Yu Ma, Xiao Feng Qian, Xiao Min Zha, Yi Zhao, Qiang Ding, Jia Zhao, Shui Wang, Jian Wu

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)687-694
Number of pages8
JournalTransplantation
Volume94
Issue number7
DOIs
StatePublished - Oct 15 2012

Fingerprint

Transplantation
Transplants
Liver
Growth
Liver Transplantation
Oxidants
Superoxide Dismutase
manganese(III)-tetrakis(4-benzoic acid)porphyrin
p38 Mitogen-Activated Protein Kinases
Graft Survival
Bromodeoxyuridine
Malondialdehyde
Serum
Alanine Transaminase
Interleukin-1
Chlorides
Regeneration
Necrosis
Tumor Necrosis Factor-alpha
Cell Count

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 journalArticle

Cui, YY, Qian, JM, Yao, AH, Ma, ZY, Qian, XF, Zha, XM, Zhao, Y, Ding, Q, Zhao, J, Wang, S & Wu, J 2012, 'SOD mimetic improves the function, growth, and survival of small-size liver grafts after transplantation in rats', Transplantation, vol. 94, no. 7, pp. 687-694. https://doi.org/10.1097/TP.0b013e3182633478
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. / SOD mimetic improves the function, growth, and survival of small-size liver grafts after transplantation in rats. In: Transplantation. 2012 ; Vol. 94, No. 7. pp. 687-694.
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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.",
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author = "Cui, {Yi Yao} and Qian, {Jian Min} and Yao, {Ai Hua} and Ma, {Zhen Yu} and Qian, {Xiao Feng} and Zha, {Xiao Min} and Yi Zhao and Qiang Ding and Jia Zhao and Shui Wang and Jian Wu",
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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.

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