In situ demonstration of improvement of liver mitochondria function by melatonin after cold ischemia.
In a previous investigation, reperfusion with a melatonin-containing medium was demonstrated to enhance bile production and tissue ATP levels in rat livers, cold-preserved with University of Wisconsin (UW) or Celsior solutions, with respect to melatonin-free reperfusion; lipid peroxidation products in the perfusate were not influenced by the indole. This was ascribed to an increased efficiency of the hepatocyte mitochondria induced by melatonin. Reactive oxygen species (ROS) normally leak from the electron transfer chain in mitochondria and excessive ROS production is presumed to mediate ischemia-reperfusion (I/R) damage. A histochemical reaction was used to demonstrate ROS on the same model. Compared to the lobular zonation of ROS in control livers, the stained area of cold-preserved livers reperfused without melatonin was restricted to a narrow portal region, in keeping with the much lower ATP content. When reperfusion was performed with melatonin, the liver morphology was improved and the ROS reaction in hepatocytes more intense, though not reaching the control liver pattern. Sinusoidal cells were poorly-stained in both cases. In conclusion, with this different approach, melatonin was confirmed to improve mitochondrial performance and to discriminate parenchymal from sinusoidal cell behavior. Our observations confirm that melatonin mitigates I/R injury and support its potential in liver transplantation.
Freitas
Isabel
I
Department of Animal Biology, CNR-IGM, University of Pavia, Italy. freitas@unipv.it
Bertone
Vittorio
V
Guarnaschelli
Catia
C
Ferrigno
Andrea
A
Boncompagni
Eleonora
E
Rizzo
Vittoria
V
Reiter
Russel J
RJ
Barni
Sergio
S
Vairetti
Mariapia
M
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D050377:Cold Ischemia; D015925:Cryopreservation; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects*; D016031:Liver Transplantation; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000502:physiology*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
D016166:Free Radical Scavengers; D007328:Insulin; D019188:Organ Preservation Solutions; D017382:Reactive Oxygen Species; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D008550:Melatonin; D000241:Adenosine; D011887:Raffinose