title: Melatonin attenuates high fat diet-induced fatty liver disease in rats.
abstract: OBJECTIVE
  To investigate melatonin's preventive action in oxidative stress in a rat model with high fat diet-induced non-alcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  NAFLD was induced by high fat diet (HFD) in adult, male, Wistar rats, weighing 180-230 g. After acclimatization for one week, they were randomly assigned to 6 experimental groups that comprised animals on regular diet plus 5 or 10 mg/kg melatonin, for 4 or 8 wk; animals on HFD, with or without 5 or 10 mg/kg melatonin, for 4 or 8 wk; and animals on HFD for 8 or 12 wk, with melatonin 10 mg/kg for the last 4 wk. Liver damage was assessed biochemically by the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histologically. Lipid peroxidation and oxidative stress were assessed by malondialdehyde and glutathione levels in liver tissue. Lipidemic indices and portal vein pressure were also measured.
  
  
  RESULTS
  Compared to rats not receiving melatonin, rats on 5 or 10 mg/kg of melatonin had lower mean liver weight (-5.0 g and -4.9 g) (P < 0.001) and lower liver weight to body weight ratio (-1.0%) (P < 0.001), for the two doses, respectively. All rats fed HFD without melatonin developed severe, grade III, steatosis. Rats on HFD with concurrent use of melatonin showed significantly less steatosis, with grade III steatosis observed in 1 of 29 (3.4%) rats on 10 mg/kg melatonin and in 3 of 27 (11.1%) rats on 5 mg/kg melatonin. Melatonin was ineffective in reversing established steatosis. Melatonin also had no effect on any of the common lipidemic serum markers, the levels of which did not differ significantly among the rats on HFD, irrespective of the use or not of melatonin. Liver cell necrosis was significantly less in rats on HFD receiving melatonin than in those not on melatonin, with the AST levels declining by a mean of 170 U/L (P = 0.01) and 224 U/L (P = 0.001), and the ALT levels declining by a mean of 62.9 U/L (P = 0.01) and 93.4 U/L (P < 0.001), for the 5 and 10 mg/kg melatonin dose, respectively. Melatonin mitigated liver damage due to peroxidation and oxidative stress in liver tissue as indicated by a significant decline in MDA production by 12.7 (P < 0.001) and 12.2 (P < 0.001) μmol/L /mg protein /mg tissue, and a significant increase in glutathione by 20.1 (P = 0.004) and 29.2 (P < 0.001) μmol/L /mg protein /mg tissue, for the 5 and 10 mg/kg melatonin dose, respectively.
  
  
  CONCLUSIONS
  Melatonin can attenuate oxidative stress, lessen liver damage, and improve liver histology in rats with high fat diet-induced NAFLD, when given concurrently with the diet.
authors.affiliation: Gregorios Hatzis, Panayiotis Ziakas, Stamatios Chatzis, Department of Pathophysiology, Athens University School of Medicine, 11527 Athens, Greece.
authors.forename: Gregorios
authors.initials: G
authors.lastname: Hatzis
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Ziakas
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kavantzas
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Triantafyllou
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Sigalas
authors.forename: Ioanna
authors.initials: I
authors.lastname: Andreadou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Ioannidis
authors.forename: Stamatios
authors.initials: S
authors.lastname: Chatzis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Filis
authors.forename: Alexandros
authors.initials: A
authors.lastname: Papalampros
authors.forename: Fragiska
authors.initials: F
authors.lastname: Sigala
keywords: Antioxidants; Lipid peroxidation; Melatonin; Metabolic syndrome; Non-alcoholic fatty liver disease; Oxidative stress; Portal vein pressure