title: Effects of polyphenol compounds melanin on NAFLD/NASH prevention.
abstract: BACKGROUND
  One of the pathogenic mechanisms of the progression non-alcoholic liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is the accumulation of reactive oxygen species (ROS). So, antioxidant therapy is necessary for successful treatment of the liver injury. We have paid attention to melanin produced by yeast Nadsoniella nigra strain X-1 as novel antioxidant and anti-inflammatory agents with low toxicity. In current study we aimed to investigate the preventive effect of melanin on the monosodium glutamate (MSG) induced NAFLD model in rats.
  
  
  METHODS
  The study was carried out on 45 Wistar rats that were divided into 3 groups: intact, MSG- and MSG+melanin groups (n=15 in each group). Newborn rats of MSG- and MSG+melanin groups were administered with MSG (4mg/g, 8μl/g, subcutaneously) at 2nd-10th days of life. Since the age of 1 month, rats of MSG-group were treated with water (0.25ml/100g), rats of MSG+melanin groups-with melanin (1mg/kg) dissolved in water (0.25ml/100g).
  
  
  BACKGROUND
  had been performed intermittently (two-week courses alternated with two-week breaks) for 3 months. In 4-month rats anthropometrical parameters and visceral adipose tissue (VAT) mass were estimated. To assess morphological changes in liver we used NAS (NAFLD activity score). The content of pro-inflammatory cytokines (interleukin (IL)-1β, IL-12Bp40, interferon (INF)-γ) and anti-inflammatory cytokines (IL-4, IL-10, tumor growth factor (TGF)-β) were measured by ELISA.
  
  
  RESULTS
  We found significantly lower total score (1.0±0.19 vs 3.33±0.36, p<0.001), degree of steatosis (0.73±0.18 vs 1.80±0.17, p<0.001) and manifestation of lobular inflammation (0.27±0.11 vs 1.20±0.17, p<0.001) due to NAFLD activity score in MSG+melanin group compared to MSG-obesity. NASH we confirmed only in 33.3% of rats with MSG-obesity that was significantly higher than after melanin (6.7%) administration (p=0.033). Melanin administration reduce amount of visceral fat on 44.5% (p<0.001) as compared to MSG-obesity group. Melanin reduced the content of IL-1β in rat serum and restored the level of anti-inflammatory cytokines (IL-10, TGF-β) to the control values.
  
  
  CONCLUSIONS
  Thus, the administration of melanin can prevent development of NAFLD/NASH in rats with MSG-induced obesity and can be considered as possible novel therapeutic agents but further studies to confirm its action needed.
authors.affiliation: Taras Shevchenko National University, Kyiv, Ukraine.
authors.forename: Natalia
authors.initials: N
authors.lastname: Belemets
authors.affiliation: Bogomolets National Medical University, Kyiv, Ukraine. Electronic address: nazariikobyliak@gmail.com.
authors.forename: Nazarii
authors.initials: N
authors.lastname: Kobyliak
authors.affiliation: Taras Shevchenko National University, Kyiv, Ukraine.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Virchenko
authors.affiliation: Taras Shevchenko National University, Kyiv, Ukraine.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Falalyeyeva
authors.affiliation: Taras Shevchenko National University, Kyiv, Ukraine.
authors.forename: Tsyryuk
authors.initials: T
authors.lastname: Olena
authors.affiliation: Bogomolets National Medical University, Kyiv, Ukraine.
authors.forename: Petro
authors.initials: P
authors.lastname: Bodnar
authors.affiliation: Taras Shevchenko National University, Kyiv, Ukraine.
authors.forename: Oleksiy
authors.initials: O
authors.lastname: Savchuk
authors.affiliation: Taras Shevchenko National University, Kyiv, Ukraine.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Galenova
authors.affiliation: 2nd Department of Internal Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Martin
authors.initials: M
authors.lastname: Caprnda
authors.affiliation: Faculty of Medicine, University of Oviedo, Central University Hospital of Asturias (HUCA), Oviedo, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Rodrigo
authors.affiliation: Department of Internal Medicine, F. D. Roosvelt Hospital, Banska Bystrica, Slovakia.
authors.forename: Lubomir
authors.initials: L
authors.lastname: Skladany
authors.affiliation: Department Pharmacology and Clinical Pharmacology, Medical Faculty, Medical University of Plovdiv, Plovdiv, Bulgaria.
authors.forename: Delian
authors.initials: D
authors.lastname: Delev
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czechia.
authors.forename: Radka
authors.initials: R
authors.lastname: Opatrilova
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czechia; 2nd Department of Surgery, Faculty of Medicine, Masaryk University, Brno, Czechia. Electronic address: kruzliakpeter@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Kruzliak
authors.affiliation: Taras Shevchenko National University, Kyiv, Ukraine.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Beregova
authors.affiliation: Taras Shevchenko National University, Kyiv, Ukraine.
authors.forename: Lyudmyla
authors.initials: L
authors.lastname: Ostapchenko
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D008543:Melanins / Q000494:pharmacology*; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D056128:Obesity, Abdominal / Q000139:chemically induced / Q000517:prevention & control; D059808:Polyphenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012970:Sodium Glutamate
chemical_list: D054392:Adipokines; D000975:Antioxidants; D016207:Cytokines; D008543:Melanins; D059808:Polyphenols; D017382:Reactive Oxygen Species; D012970:Sodium Glutamate
keywords: Cytokines; Inflammation; Melanin; Non-alcoholic liver disease (NAFLD); Nonalcoholic steatohepatitis (NASH); Reactive oxygen species (ROS); Therapy