Faculty Collaboration Database

Pyruvate inhibits hepatic ischemia-reperfusion injury in rats. Transplantation 2001 Jul 15;72(1):27-30

Date

07/27/2001

Pubmed ID

11468530

DOI

10.1097/00007890-200107150-00008

Scopus ID

2-s2.0-0035879279 (requires institutional sign-in at Scopus site)   51 Citations

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.

Author List

Sileri P, Schena S, Morini S, Rastellini C, Pham S, Benedetti E, Cicalese L

Author

Stefano Schena MD, PhD Associate Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Ischemia
Liver
Liver Circulation
Male
Pyruvic Acid
Rats
Rats, Inbred ACI
Reperfusion Injury
Survival Analysis
Time Factors