Melatonin protects from, but does not reverse, the effects of mediators of sepsis on liver bioenergetics.
BACKGROUND
Reactive oxygen species (ROS) have been reported to play a significant role in the pathogenesis of sepsis and liver dysfunction. In particular, neonates are at risk for sepsis and have less protection against oxidation. Melatonin has been reported to reduce the oxidative stress status in neonates with sepsis. Little is known about the effect of melatonin on liver bioenergetics. The aim of this study was to investigate the protective effect of melatonin on hepatocyte oxidative energy metabolism against hydrogen peroxide (H2O2), a free radical mediator of septic damage.


METHODS
Hepatocytes were isolated from neonatal suckling rats (11-15 days old). The cells, respiring on palmitate, were exposed to H2O2 at the concentration of 2 mmol/l, melatonin alone at 1 micromol/l or 10 micromol/l, or H2O2 plus melatonin at each of the two concentrations. Oxygen consumption was measured polarographically. In subsequent experiments, melatonin was added after the hydrogen peroxide.


RESULTS
Hydrogen peroxide significantly reduced hepatocyte oxygen consumption ( p<0.001), but melatonin added at the same time was able to prevent this effect ( p<0.001). However, melatonin at a low dose significantly inhibited hepatocyte oxygen consumption ( p<0.001), an effect which has not been previously described. When melatonin was added to cells after they had been exposed to hydrogen peroxide, a beneficial effect was not observed, indicating that melatonin is not able to reverse the effects of hydrogen peroxide.


CONCLUSIONS
Melatonin has a protective effect on hepatocyte oxidative metabolism, improving mitochondrial function by counteracting oxidative stress.
Basile
Marina
M
Department of Medical and Surgical Pediatric Sciences, University of Messina, Via Consolare Valeria-Gazzi, 98124 Messina, Italy.
Romeo
Carmelo
C
Gitto
Eloisa
E
Spitz
Lewis
L
Pierro
Agostino
A
Eaton
Simon
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D018929:Cell Culture Techniques; D004734:Energy Metabolism / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology*; D023421:Models, Animal; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000378:metabolism*
D000975:Antioxidants; D018836:Inflammation Mediators; D016877:Oxidants; D006861:Hydrogen Peroxide; D008550:Melatonin