Oxidative damage in the liver induced by ischemia-reperfusion: protection by melatonin.
OBJECTIVE
The protective effect of mela tonin 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.


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.
Sewerynek
E
E
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio 78284, USA.
Reiter
R J
RJ
Melchiorri
D
D
Ortiz
G G
GG
Lewinski
A
A
D000818:Animals; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008550:Melatonin