Oxidative damage in the liver induced by ischemia-reperfusion: Protection by melatonin

Ewa Sewerynek, Russel J. Reiter, Daniela Melchiorri, Genaro G. Ortiz, Andrzej Lewinski

Research output: Contribution to journalArticlepeer-review

245 Scopus citations


Background/Aims: The protective effect of melatonin against the damage inflicted by reactive oxygen species during liver ischemia-reperfusion was investigated in male Sprague-Dawley rats using both biochemical and morphological parameters. Materials and Methods: For biochemical analyses the levels of lipid peroxidation products [malonaldehyde (MDA) + 4-hydroxyalkenals (4-HDA)] levels of reduced glutathione (GSH) and oxidized glutathione (GSSG), and the activities of GSH peroxidase (GSH-Px), GSH reductase (GSSG-Rd) and glucose-6-phosphatase (G6Pase) were estimated. Also the number of polymorphonuclear neutrophils (PMNs) in injured livers was counted in histological sections. Results: After 40 min of ischemia followed by 60 min of reperfusion the hepatic levels of MDA + 4-HDA increased. Pretreatment of the animals with melatonin abolished the rise in MDA + 4-HDA induced by ischemia-reperfusion. GSH concentrations decreased and GSSG increased during ischemia-reperfusion and, again melatonin counteracted these changes. Additionally, the activities of two antioxidative enzymes (GSH-Px and GSSG-Rd) decreased during the experimental period with melatonin preventing the change in GSSG-Rd. G6Pase activity was not influenced by either ischemia-reperfusion or by melatonin administration. Morphologically, PMN infiltration was obvious in the ischemia-reperfusion damaged liver, a change also partially reversed by melatonin. Conclusions: In this model of liver ischemia-reperfusion injury, exogenously administered melatonin effectively protected against oxidative damage. The hepatic parameters which illustrated this protection were reduced lipid peroxidation products, lowered PMN infiltration, increased GSH and reduced GSSG levels, and elevated GSSG-Rd activity all of which were observed in melatonin-treated rats in which damage due to ischemia-reperfusion had been induced.

Original languageEnglish (US)
Pages (from-to)898-905
Number of pages8
Issue number10
StatePublished - 1996


  • Free radical damage to liver
  • Glutathione metabolism
  • Lipid peroxidation
  • Melatonin as an antioxidant
  • Polymorphonuclear infiltration

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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