Dataset Information

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.

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.

SUBMITTER: Cui YY

PROVIDER: S-EPMC3465521 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Cui Yi-Yao YY Qian Jian-Min JM Yao Ai-Hua AH Ma Zhen-Yu ZY Qian Xiao-Feng XF Zha Xiao-Min XM Zhao Yi Y Ding Qiang Q Zhao Jia J Wang Shui S Wu Jian J

Transplantation 20121001 7

<h4>Background</h4>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.<h4>Aims</h4>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 ...[more]

PMID: 22955229

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Project description:The present study aimed to explore whether heme oxygenase-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) have a protective effect on liver transplantation with steatotic liver grafts in rats, and to determine the role of the intestinal microbiota in such protection. HO-1/BMMSCs were obtained by transduction of Hmox1 gene [encoding heme oxygenase (HO-1)]-encoding adenoviruses into primary rat BMMSCs. Steatotic livers were obtained by feeding rats a high-fat diet, and a model of liver transplantation with steatotic liver grafts was established. The recipients were treated with BMMSCs, HO-1/BMMSCs, or neither, via the portal vein. Two time points were used: postoperative day 1 (POD 1) and POD 7. The results showed that under the effect of HO-1/BMMSCs, the degree of steatosis in the liver grafts was significantly reduced, and the level of liver enzymes and the levels of pro-inflammatory cytokines in plasma were reduced. The effect of HO-1/BMMSCs was better than that of pure BMMSCs in the prolongation of the rats' postoperative time. In addition, HO-1/BMMSCs promoted the recovery of recipients' intestinal structure and function, especially on POD 7. The intestinal villi returned to normal, the expression of tight junction proteins was restored, and intestinal permeability was reduced on POD 7. The intestinal bacterial of the LT group showed significantly weakened energy metabolism and overgrowth. On POD 1, the abundance of Akkermansiaceae was higher. On POD 7, the abundance of Clostridiaceae increased, the level of lipopolysaccharide increased, the intestinal mucosal barrier function was destroyed, and the levels of several invasive bacteria increased. When treated with HO-1/BMMSCs, the energy metabolism of intestinal bacteria was enhanced, and on POD 1, levels bacteria that protect the intestinal mucosa, such as Desulfovibrionaceae, increased significantly. On POD 7, the changed intestinal microbiota improved lipid metabolism and increased the levels of butyrate-producing bacteria, such as Lachnospiraceae. In conclusion, HO-1/BMMSCs have protective effects on steatotic liver grafts and the intestinal barrier function of the recipients. By improving lipid metabolism and increasing the abundance of butyrate-producing bacteria, the changed intestinal microbiota has a protective effect and prolongs the recipients' survival time.

Project description:There are limited data on liver transplant (LT) outcomes with grafts from super obese donors. The present study aims to evaluate a unique cohort of recipients following LT using grafts from donors with body mass index (BMI) ≥50.MethodsPatients receiving grafts from donors with BMI ≥50 and BMI <50 from 2010 to 2019 were identified. A 1:2 case-control match was conducted to compare outcomes between the groups. Survival was analyzed using the Kaplan-Meier curves.ResultsSix hundred sixty-five adult LTs were performed in the study period. Eighteen patients receiving a graft from a donor with BMI ≥50 were identified and matched to 36 patients receiving a graft from a donor with BMI <50. Grafts from male donors were significantly lower in the donor BMI ≥50 group when compared with the donor BMI <50 group (16.7% versus 66.7%, P = 0.001). Liver biopsy was performed in 77.8% of grafts in the donor BMI ≥50 group, whereas only in 38.8% of the grafts in the donor BMI <50 group (P = 0.007). Recipients in the donor BMI ≥50 group had a significantly higher diagnosis rate of hepatocellular carcinoma pretransplant versus the donor BMI <50 group (38.9% versus 8.3%, respectively; P = 0.006). Major complications within 30 d did not differ statistically between groups. Biliary complications within the first 30 d were equal among groups (16.7%). Subanalysis comparing the super obese donor group versus the nonobese donor group showed no differences in terms of postoperative complications, readmission rate, graft rejection, or major complications including the need for reoperation, retransplantation, or mortality. Graft and patient survival at 1-, 3-, and 5-y graft were similar between the donor BMI ≥50 group versus donor BMI <50 group (94%/89%/89% versus 88%/88%/88%, P = 0.89, and 94%/94%/94% versus 88%/88%/88%, P = 0.48, respectively).ConclusionsLT with carefully selected grafts from super obese donors can be safely performed with outcomes comparable with non-super obese donor livers. Therefore, these types of grafts could represent a safe means to expand the donor pool.

Dataset Information

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

Background

Aims

Methods

Results

Conclusions

Publications

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

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