title: Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis.
abstract: BACKGROUND
  Nonalcoholic fatty liver disease is a chronic metabolic disorder with significant impact on cardiovascular and liver mortality.
  
  
  OBJECTIVE
  In this study, we examined the effects of silibinin on liver and myocardium injury in an experimental model of nonalcoholic fatty liver disease.
  
  
  METHODS
  A four-week daily dose of silibinin (20 mg/kg i.p.) was administrated to db/db mice fed a methionine-choline deficient diet. Hepatic and myocardial histology, oxidative stress and inflammatory cytokines were evaluated.
  
  
  RESULTS
  Silibinin administration decreased HOMA-IR, serum ALT and markedly improved hepatic and myocardial damage. Silibinin reduced isoprostanes, 8-deoxyguanosine and nitrites/nitrates in the liver and in the heart of db/db fed the methionine-choline deficient diet, whereas glutathione levels were restored to lean mice levels in both tissues. Consistently, liver mitochondrial respiratory chain activity was significantly impaired in untreated mice and was completely restored in silibinin-treated animals. TNF-α was increased whereas IL-6 was decreased both in the liver and heart of db/db fed methionine-choline deficient diet. Silibinin reversed heart TNF-α and IL-6 expression to control mice levels. Indeed, liver JNK phosphorylation was reduced to control levels in treated animals.
  
  
  CONCLUSIONS
  This study demonstrates a combined effectiveness of silibinin on improving liver and myocardial injury in experimental nonalcoholic fatty liver disease.
authors.affiliation: Department of Internal Medicine, University of Catania, Catania, Italy. federicosalamone@yahoo.it
authors.forename: Federico
authors.initials: F
authors.lastname: Salamone
authors.forename: Fabio
authors.initials: F
authors.lastname: Galvano
authors.forename: Antonella
authors.initials: A
authors.lastname: Marino Gammazza
authors.forename: Antonella
authors.initials: A
authors.lastname: Marino
authors.forename: Claudia
authors.initials: C
authors.lastname: Paternostro
authors.forename: Daniele
authors.initials: D
authors.lastname: Tibullo
authors.forename: Fabio
authors.initials: F
authors.lastname: Bucchieri
authors.forename: Andrea
authors.initials: A
authors.lastname: Mangiameli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Parola
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002796:Choline Deficiency / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004032:Diet; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D007333:Insulin Resistance; D028421:Isoprostanes / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008715:Methionine / Q000172:deficiency; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology / Q000627:therapeutic use*; D018709:Statistics, Nonparametric
chemical_list: D000975:Antioxidants; D016207:Cytokines; D028421:Isoprostanes; D009566:Nitrates; D009573:Nitrites; D012838:Silymarin; D000077385:Silybin; D008715:Methionine; D000410:Alanine Transaminase; D048031:JNK Mitogen-Activated Protein Kinases; D005978:Glutathione