Pyruvate inhibits hepatic ischemia-reperfusion injury in rats

Pierpaolo Sileri, Stefano Schena, Sergio Morini, Cristiana Rastellini, Si Pham, Enrico Benedetti, Luca Cicalese

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Background. Ischemia/reperfusion (I/R) injury is a limiting factor in liver transplantation. We have recently shown that pyruvate (PY) inhibits intestinal and renal I/R injury. This study aims to evaluate the protective effect of PY on hepatic I/R injury. Methods. ACI rats were treated with PY, whereas control animals received placebo. Rats were killed after 60 min of partial hepatic ischemia and after 2, 6, 24, and 48 hr of reperfusion. For each time point, serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were measured, and liver biopsy specimens were obtained to evaluate morphology, DNA fragmentation, and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling). Results. The survival rate 48 hr after I/R was 83% in the control group, and 100% in the PY-treated group (P>0.05). Increased enzymatic levels and histologic findings showed increased liver damage in the untreated group compared with PY. In control rats, apoptosis was enhanced after 1 hr of ischemia and peaked after 2 hr of reperfusion, to decrease gradually 48 hr after reperfusion; in the PY group apoptosis was delayed and reduced. After 1 hr of ischemia, the number of apoptotic nuclei was significantly increased in control livers compared with normal preischemic livers, whereas the number was significantly reduced by PY. After 2 hr of reperfusion, the maximum number of apoptotic cells was observed, whereas PY significantly reduced the amount of apoptotic cells (P<0.05). Apoptosis was delayed in PY-treated livers to 6 hr after reperfusion, peaking at a significantly lower count compared with placebo-treated controls (P<0.05). Conclusion. These data indicate that PY has a protective effect on I/R injury of the liver.

Original languageEnglish (US)
Pages (from-to)27-30
Number of pages4
JournalTransplantation
Volume72
Issue number1
DOIs
StatePublished - Jul 15 2001
Externally publishedYes

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Reperfusion Injury
Pyruvic Acid
Liver
Reperfusion
Ischemia
Apoptosis
Inbred ACI Rats
Placebos
DNA Nucleotidylexotransferase
DNA Fragmentation
Biotin
Aspartate Aminotransferases
Alanine Transaminase
L-Lactate Dehydrogenase
Liver Transplantation
Cell Count
Kidney
Biopsy
Control Groups

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Sileri, P., Schena, S., Morini, S., Rastellini, C., Pham, S., Benedetti, E., & Cicalese, L. (2001). Pyruvate inhibits hepatic ischemia-reperfusion injury in rats. Transplantation, 72(1), 27-30. https://doi.org/10.1097/00007890-200107150-00008

Pyruvate inhibits hepatic ischemia-reperfusion injury in rats. / Sileri, Pierpaolo; Schena, Stefano; Morini, Sergio; Rastellini, Cristiana; Pham, Si; Benedetti, Enrico; Cicalese, Luca.

In: Transplantation, Vol. 72, No. 1, 15.07.2001, p. 27-30.

Research output: Contribution to journalArticle

Sileri, P, Schena, S, Morini, S, Rastellini, C, Pham, S, Benedetti, E & Cicalese, L 2001, 'Pyruvate inhibits hepatic ischemia-reperfusion injury in rats', Transplantation, vol. 72, no. 1, pp. 27-30. https://doi.org/10.1097/00007890-200107150-00008
Sileri P, Schena S, Morini S, Rastellini C, Pham S, Benedetti E et al. Pyruvate inhibits hepatic ischemia-reperfusion injury in rats. Transplantation. 2001 Jul 15;72(1):27-30. https://doi.org/10.1097/00007890-200107150-00008
Sileri, Pierpaolo ; Schena, Stefano ; Morini, Sergio ; Rastellini, Cristiana ; Pham, Si ; Benedetti, Enrico ; Cicalese, Luca. / Pyruvate inhibits hepatic ischemia-reperfusion injury in rats. In: Transplantation. 2001 ; Vol. 72, No. 1. pp. 27-30.
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AU - Benedetti, Enrico

AU - Cicalese, Luca

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AB - Background. Ischemia/reperfusion (I/R) injury is a limiting factor in liver transplantation. We have recently shown that pyruvate (PY) inhibits intestinal and renal I/R injury. This study aims to evaluate the protective effect of PY on hepatic I/R injury. Methods. ACI rats were treated with PY, whereas control animals received placebo. Rats were killed after 60 min of partial hepatic ischemia and after 2, 6, 24, and 48 hr of reperfusion. For each time point, serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were measured, and liver biopsy specimens were obtained to evaluate morphology, DNA fragmentation, and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling). Results. The survival rate 48 hr after I/R was 83% in the control group, and 100% in the PY-treated group (P>0.05). Increased enzymatic levels and histologic findings showed increased liver damage in the untreated group compared with PY. In control rats, apoptosis was enhanced after 1 hr of ischemia and peaked after 2 hr of reperfusion, to decrease gradually 48 hr after reperfusion; in the PY group apoptosis was delayed and reduced. After 1 hr of ischemia, the number of apoptotic nuclei was significantly increased in control livers compared with normal preischemic livers, whereas the number was significantly reduced by PY. After 2 hr of reperfusion, the maximum number of apoptotic cells was observed, whereas PY significantly reduced the amount of apoptotic cells (P<0.05). Apoptosis was delayed in PY-treated livers to 6 hr after reperfusion, peaking at a significantly lower count compared with placebo-treated controls (P<0.05). Conclusion. These data indicate that PY has a protective effect on I/R injury of the liver.

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