Exogenous melatonin enhances bile flow and ATP levels after cold storage and reperfusion in rat liver: Implications for liver transplantation

Mariapia Vairetti, Andrea Ferrigno, Roberta Bertone, Vittoria Rizzo, Plinio Richelmi, Francantonio Bertè, Russel J. Reiter, Isabel Freitas

Research output: Contribution to journalArticle

Abstract

Although the use of melatonin in the transplantation field has been suggested, it has not been previously tested in a liver cold-storage model. We used a rat liver model to study (a) the dose-dependent effect of melatonin on bile production, and (b) the potential of melatonin to improve liver function after cold-storage. Male Wistar rats were perfused with KrebsHenseleit bicarbonate buffer (KHB) at 37°C without or with 25, 50, 100 and 200 μM melatonin. Each dose of melatonin stimulated bile production. For cold-storage studies, livers were flushed with either University of Wisconsin (UW) or Celsior solution and stored for 20 hr at 4°C. Reperfusion (120 min) was performed with KHB at 37°C. In subsequent studies, 100 μM melatonin were added to the perfusate during the reperfusion period. ATP and melatonin levels in the tissue were measured. Bile analysis was performed by measuring melatonin, bilirubin and gamma-glutamyl transpeptidase (γ-GT) levels in the fluid. A dose-dependent increase in bile secretion, associated with an enhanced melatonin and bilirubin levels in the bile were observed. Also, tissue levels of melatonin increased in a dose-dependent manner. When melatonin was added during the reperfusion period, bile production and bile bilirubin levels increased both with UW and Celsior solutions. The analysis of γ-GT in the bile showed an increase in the Celsior-preserved liver and the addition of melatonin to the perfusate reduced this effect. Tissue ATP levels were higher when melatonin was added to the perfusion medium. Higher levels of melatonin in bile than in tissue were found. In conclusion, we demonstrate that melatonin improves significantly the restoration of liver function after cold-storage and reperfusion.

Original languageEnglish
Pages (from-to)223-230
Number of pages8
JournalJournal of Pineal Research
Volume38
Issue number4
DOIs
Publication statusPublished - May 2005

Fingerprint

Melatonin
Bile
Liver Transplantation
Reperfusion
Adenosine Triphosphate
Liver
Bilirubin
Bicarbonates
Buffers
gamma-Glutamyltransferase
Wistar Rats

Keywords

  • ATP
  • Bile
  • Cold storage
  • Liver
  • Melatonin
  • Organ transplantation
  • Reperfusion

ASJC Scopus subject areas

  • Endocrinology

Cite this

Exogenous melatonin enhances bile flow and ATP levels after cold storage and reperfusion in rat liver : Implications for liver transplantation. / Vairetti, Mariapia; Ferrigno, Andrea; Bertone, Roberta; Rizzo, Vittoria; Richelmi, Plinio; Bertè, Francantonio; Reiter, Russel J.; Freitas, Isabel.

In: Journal of Pineal Research, Vol. 38, No. 4, 05.2005, p. 223-230.

Research output: Contribution to journalArticle

Vairetti, Mariapia ; Ferrigno, Andrea ; Bertone, Roberta ; Rizzo, Vittoria ; Richelmi, Plinio ; Bertè, Francantonio ; Reiter, Russel J. ; Freitas, Isabel. / Exogenous melatonin enhances bile flow and ATP levels after cold storage and reperfusion in rat liver : Implications for liver transplantation. In: Journal of Pineal Research. 2005 ; Vol. 38, No. 4. pp. 223-230.
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AU - Bertone, Roberta

AU - Rizzo, Vittoria

AU - Richelmi, Plinio

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AB - Although the use of melatonin in the transplantation field has been suggested, it has not been previously tested in a liver cold-storage model. We used a rat liver model to study (a) the dose-dependent effect of melatonin on bile production, and (b) the potential of melatonin to improve liver function after cold-storage. Male Wistar rats were perfused with KrebsHenseleit bicarbonate buffer (KHB) at 37°C without or with 25, 50, 100 and 200 μM melatonin. Each dose of melatonin stimulated bile production. For cold-storage studies, livers were flushed with either University of Wisconsin (UW) or Celsior solution and stored for 20 hr at 4°C. Reperfusion (120 min) was performed with KHB at 37°C. In subsequent studies, 100 μM melatonin were added to the perfusate during the reperfusion period. ATP and melatonin levels in the tissue were measured. Bile analysis was performed by measuring melatonin, bilirubin and gamma-glutamyl transpeptidase (γ-GT) levels in the fluid. A dose-dependent increase in bile secretion, associated with an enhanced melatonin and bilirubin levels in the bile were observed. Also, tissue levels of melatonin increased in a dose-dependent manner. When melatonin was added during the reperfusion period, bile production and bile bilirubin levels increased both with UW and Celsior solutions. The analysis of γ-GT in the bile showed an increase in the Celsior-preserved liver and the addition of melatonin to the perfusate reduced this effect. Tissue ATP levels were higher when melatonin was added to the perfusion medium. Higher levels of melatonin in bile than in tissue were found. In conclusion, we demonstrate that melatonin improves significantly the restoration of liver function after cold-storage and reperfusion.

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KW - Organ transplantation

KW - Reperfusion

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