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Pediatr Surg Int (2004) 20: 263266 DOI 10.1007/s00383-003-1123-1
ORIGINAL ARTICLE
Marina Basile Carmelo Romeo Eloisa Gitto Lewis Spitz Agostino Pierro Simon Eaton
Melatonin protects from, but does not reverse, the effects of mediators of sepsis on liver bioenergetics
Published online: 4 February 2004 Springer-Verlag 2004
Abstract Background: Reactive oxygen species (ROS) have been reported to play a signicant 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 eect of melatonin on liver bioenergetics. The aim of this study was to investigate the protective eect 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 (1115 days old). The cells, respiring on palmitate, were exposed to H2O2 at the concentration of 2 mmol/l, melatonin alone at 1 lmol/l or 10 lmol/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 signicantly reduced hepatocyte oxygen consumption (p<0.001), but melatonin added at the same time was able to prevent this eect (p<0.001). However, melatonin at a low dose signicantly inhibited hepatocyte oxygen consumption (p<0.001), an eect which has not been previously described. When melatonin was added to cells after they had been exposed to hydrogen peroxide, a benecial eect was not observed, indicating that melatonin is not able to reverse the eects of hydrogen peroxide.
Conclusion: Melatonin has a protective eect on hepatocyte oxidative metabolism, improving mitochondrial function by counteracting oxidative stress.
Keywords Neonate Sepsis Hydrogen peroxide Melatonin Oxidative stress Surgery
Introduction Sepsis remains a major cause of morbidity and mortality in adults [1], children [2] and neonates [3]. Increased risk factors for sepsis in the neonatal period include prematurity [4], low birth weight [5], surgery [3], requirement for mechanical ventilation [6], the use of parenteral nutrition [7] and the presence of abnormal gastrointestinal ora [8, 9]. Much of the mortality associated with neonatal sepsis is due to multiple-organ-system failure (hepaticrenalcardiacpulmonarymicrovascular) [10, 11, 12], as in adults [13]. Suitable...