Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation

K. Hashimoto, T. Nishizaki, T. Yoshizumi, H. Uchiyama, S. Okano, T. Ikegami, K. Yanaga, K. Sugimachi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background. Proinflammatory cytokines such as interleukin 1-β (IL-1β) and tumor necrosis factor-α (TNF-α) play an important role in the development of hepatic ischemia/reperfusion injury. FR167653 has been characterized as a potent suppressant of IL-1β and TNF-α production. The aim of this study was to evaluate the effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation. Methods. Donor livers were preserved with cold University of Wisconsin solution for 48 hr and transplanted orthotopically. Immediately after reperfusion, FR167653 (1 mg/kg, FR-treated group) or normal saline solution (control group) was administered i.v.. The severity of liver injury was determined by hepatic enzyme levels as well as by histological findings. The accumulation of IL-1β and TNF-α mRNA in the liver was analyzed by semi-quantitative reverse transcription-polymerase chain reaction. Tissue factor expression was subjected to immunohistochemical analysis. Results. In the FR-treated group, release of aspartate aminotransferase and alanine aminotransferase after reperfusion was significantly lower (P<0.05 and P<0.02, respectively), and histological liver injury was less prominent, than in the control group. Accumulation of IL-1β and TNF-α mRNA was suppressed in the FR-treated liver. Tissue factor expression on Kupffer cells and sinusoidal endothelial cells, marked in the control group, was almost absent in the FR-treated group. Seven-day survival in the FR-treated group (75%) was significantly better than that in the control group (12.5%) (P<0.01). Conclusions. These results indicate that treatment with FR167653 ameliorates cold ischemia/reperfusion injury in liver transplantation.

Original languageEnglish
Pages (from-to)1318-1322
Number of pages5
JournalTransplantation
Volume70
Issue number9
DOIs
Publication statusPublished - Nov 15 2000

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Cold Ischemia
Reperfusion Injury
Liver Transplantation
Interleukin-1
Liver
Tumor Necrosis Factor-alpha
Control Groups
Thromboplastin
Reperfusion
Messenger RNA
Kupffer Cells
Wounds and Injuries
Aspartate Aminotransferases
FR 167653
Alanine Transaminase
Sodium Chloride
Reverse Transcription
Endothelial Cells
Cytokines
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation. / Hashimoto, K.; Nishizaki, T.; Yoshizumi, T.; Uchiyama, H.; Okano, S.; Ikegami, T.; Yanaga, K.; Sugimachi, K.

In: Transplantation, Vol. 70, No. 9, 15.11.2000, p. 1318-1322.

Research output: Contribution to journalArticle

Hashimoto, K. ; Nishizaki, T. ; Yoshizumi, T. ; Uchiyama, H. ; Okano, S. ; Ikegami, T. ; Yanaga, K. ; Sugimachi, K. / Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation. In: Transplantation. 2000 ; Vol. 70, No. 9. pp. 1318-1322.
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abstract = "Background. Proinflammatory cytokines such as interleukin 1-β (IL-1β) and tumor necrosis factor-α (TNF-α) play an important role in the development of hepatic ischemia/reperfusion injury. FR167653 has been characterized as a potent suppressant of IL-1β and TNF-α production. The aim of this study was to evaluate the effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation. Methods. Donor livers were preserved with cold University of Wisconsin solution for 48 hr and transplanted orthotopically. Immediately after reperfusion, FR167653 (1 mg/kg, FR-treated group) or normal saline solution (control group) was administered i.v.. The severity of liver injury was determined by hepatic enzyme levels as well as by histological findings. The accumulation of IL-1β and TNF-α mRNA in the liver was analyzed by semi-quantitative reverse transcription-polymerase chain reaction. Tissue factor expression was subjected to immunohistochemical analysis. Results. In the FR-treated group, release of aspartate aminotransferase and alanine aminotransferase after reperfusion was significantly lower (P<0.05 and P<0.02, respectively), and histological liver injury was less prominent, than in the control group. Accumulation of IL-1β and TNF-α mRNA was suppressed in the FR-treated liver. Tissue factor expression on Kupffer cells and sinusoidal endothelial cells, marked in the control group, was almost absent in the FR-treated group. Seven-day survival in the FR-treated group (75{\%}) was significantly better than that in the control group (12.5{\%}) (P<0.01). Conclusions. These results indicate that treatment with FR167653 ameliorates cold ischemia/reperfusion injury in liver transplantation.",
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T1 - Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation

AU - Hashimoto, K.

AU - Nishizaki, T.

AU - Yoshizumi, T.

AU - Uchiyama, H.

AU - Okano, S.

AU - Ikegami, T.

AU - Yanaga, K.

AU - Sugimachi, K.

PY - 2000/11/15

Y1 - 2000/11/15

N2 - Background. Proinflammatory cytokines such as interleukin 1-β (IL-1β) and tumor necrosis factor-α (TNF-α) play an important role in the development of hepatic ischemia/reperfusion injury. FR167653 has been characterized as a potent suppressant of IL-1β and TNF-α production. The aim of this study was to evaluate the effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation. Methods. Donor livers were preserved with cold University of Wisconsin solution for 48 hr and transplanted orthotopically. Immediately after reperfusion, FR167653 (1 mg/kg, FR-treated group) or normal saline solution (control group) was administered i.v.. The severity of liver injury was determined by hepatic enzyme levels as well as by histological findings. The accumulation of IL-1β and TNF-α mRNA in the liver was analyzed by semi-quantitative reverse transcription-polymerase chain reaction. Tissue factor expression was subjected to immunohistochemical analysis. Results. In the FR-treated group, release of aspartate aminotransferase and alanine aminotransferase after reperfusion was significantly lower (P<0.05 and P<0.02, respectively), and histological liver injury was less prominent, than in the control group. Accumulation of IL-1β and TNF-α mRNA was suppressed in the FR-treated liver. Tissue factor expression on Kupffer cells and sinusoidal endothelial cells, marked in the control group, was almost absent in the FR-treated group. Seven-day survival in the FR-treated group (75%) was significantly better than that in the control group (12.5%) (P<0.01). Conclusions. These results indicate that treatment with FR167653 ameliorates cold ischemia/reperfusion injury in liver transplantation.

AB - Background. Proinflammatory cytokines such as interleukin 1-β (IL-1β) and tumor necrosis factor-α (TNF-α) play an important role in the development of hepatic ischemia/reperfusion injury. FR167653 has been characterized as a potent suppressant of IL-1β and TNF-α production. The aim of this study was to evaluate the effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation. Methods. Donor livers were preserved with cold University of Wisconsin solution for 48 hr and transplanted orthotopically. Immediately after reperfusion, FR167653 (1 mg/kg, FR-treated group) or normal saline solution (control group) was administered i.v.. The severity of liver injury was determined by hepatic enzyme levels as well as by histological findings. The accumulation of IL-1β and TNF-α mRNA in the liver was analyzed by semi-quantitative reverse transcription-polymerase chain reaction. Tissue factor expression was subjected to immunohistochemical analysis. Results. In the FR-treated group, release of aspartate aminotransferase and alanine aminotransferase after reperfusion was significantly lower (P<0.05 and P<0.02, respectively), and histological liver injury was less prominent, than in the control group. Accumulation of IL-1β and TNF-α mRNA was suppressed in the FR-treated liver. Tissue factor expression on Kupffer cells and sinusoidal endothelial cells, marked in the control group, was almost absent in the FR-treated group. Seven-day survival in the FR-treated group (75%) was significantly better than that in the control group (12.5%) (P<0.01). Conclusions. These results indicate that treatment with FR167653 ameliorates cold ischemia/reperfusion injury in liver transplantation.

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