title: Whey-hydrolyzed peptide-enriched immunomodulating diet prevents progression of liver cirrhosis in rats.
abstract: OBJECTIVE
  Liver fibrosis and subsequent cirrhosis is a major cause of death worldwide, but few effective antifibrotic therapies are reported. Whey-hydrolyzed peptide (WHP), a major peptide component of bovine milk, exerts anti-inflammatory effects in experimental models. A WHP-enriched diet is widely used for immunomodulating diets (IMD) in clinical fields. However, the effects of WHP on liver fibrosis remain unknown. The aim of this study was to investigate the antifibrotic effects of WHP in a rat cirrhosis model.
  
  
  METHODS
  Progressive liver fibrosis was induced by repeated intraperitoneal administration of dimethylnitrosamine (DMN) for 3 wk. Rats were fed either a WHP-enriched IMD (WHP group) or a control enteral diet (control group). The degree of liver fibrosis was compared between groups. Hepatocyte-protective effects were examined using hepatocytes isolated from rats fed a WHP diet. Reactive oxygen species and glutathione in liver tissue were investigated in the DMN cirrhosis model.
  
  
  RESULTS
  Macroscopic and microscopic progression of liver fibrosis was remarkably suppressed in the WHP group. Elevated serum levels of liver enzymes and hyaluronic acid, and liver tissue hydroxyproline content were significantly attenuated in the WHP group. Necrotic hepatocyte rates with DMN challenge, isolated from rats fed a WHP-enriched IMD, were significantly lower. In the DMN cirrhosis model, reactive oxygen species were significantly lower, and glutathione was significantly higher in the WHP group's whole liver tissue.
  
  
  CONCLUSIONS
  A WHP-enriched IMD effectively prevented progression of DMN-induced liver fibrosis in rats via a direct hepatocyte-protective effect and an antioxidant effect through glutathione synthesis.
authors: Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Kanta
authors: K
authors: Jobara
authors: Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: Kaido@kuhp.kyoto-u.ac.jp.
authors: Toshimi
authors: T
authors: Kaido
authors: Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Tomohide
authors: T
authors: Hori
authors: Department of Target Therapy Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Keiko
authors: K
authors: Iwaisako
authors: Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Kosuke
authors: K
authors: Endo
authors: Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Yoichiro
authors: Y
authors: Uchida
authors: Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Shinji
authors: S
authors: Uemoto
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002417:Cattle; D004128:Dimethylnitrosamine; D018450:Disease Progression; D005978:Glutathione / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000178:diet therapy* / Q000473:pathology; D008297:Male; D008894:Milk Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D009336:Necrosis; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067816:Whey Proteins
chemical_list: D000975:Antioxidants; D008894:Milk Proteins; D010455:Peptides; D017382:Reactive Oxygen Species; D000067816:Whey Proteins; D006820:Hyaluronic Acid; D005978:Glutathione; D004128:Dimethylnitrosamine; D006909:Hydroxyproline
keywords: Antifibrotic; Cirrhosis; Hepatocytes-protective; Immunomodulating diet; Liver fibrosis; Whey-hydrolyzed peptide