title: Polaprezinc prevents ongoing thioacetamide-induced liver fibrosis in rats.
abstract: OBJECTIVE
  Cirrhotic patients commonly have a liver zinc deficiency, which may aggravate liver fibrosis due to the lack of antioxidative effects of zinc. This study examined the ability of polaprezinc, N-(3-aminopropionyl)-l-histidinato zinc, to prevent fibrosis in a rat model of thioacetamide (TAA)-induced hepatic fibrosis.
  
  
  METHODS
  Liver cirrhosis was induced by orally administering TAA for 20 weeks. The rats were cotreated with one of the following for the last 10 weeks of TAA treatment: (1) polaprezinc (50 or 200mg/kg/day); (2) l-carnosine (155 mg/kg/day), which contained equal amounts of l-carnosine as 200mg/kg/day polaprezinc; (3) zinc sulfate (112 mg/kg/day) or (4) zinc-l-aspartic complex (317.8 mg/kg/day). Both zinc supplementations contained equal amounts of zinc as high-dose polaprezinc.
  
  
  RESULTS
  Hepatic zinc levels fell significantly in rats treated with TAA for 20 weeks. Cotreating with high-dose polaprezinc and zinc-l-aspartic complex for 10 weeks prevented hepatic zinc loss. Hepatic hydroxyproline and tissue inhibitor of metalloproteinases-1 (TIMP-1) were significantly higher in rats treated with TAA for 20 weeks than 10 weeks, whereas polaprezinc prevented changes in these fibrosis markers and reduced hepatic transforming growth factor-β1 protein concentration, macroscopic and histologic changes. TAA caused oxidative stress-related changes in the liver that were prevented by high-dose polaprezinc and partially by zinc-l-aspartic complex. Treatment with l-carnosine, low-dose polaprezinc or zinc sulfate for 10 weeks did not affect liver fibrosis progression or oxidative stress-related changes.
  
  
  CONCLUSIONS
  Polaprezinc may prevent ongoing fibrosis by preventing zinc depletion, oxidative stress and fibrosis markers in cirrhotic livers.
authors.affiliation: Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa, Hokkaido 078-8510, Japan. kono@asahikawa-med.ac.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Kono
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Asama
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Chisato
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ebisawa
authors.forename: Taishi
authors.initials: T
authors.lastname: Okayama
authors.forename: Kouji
authors.initials: K
authors.lastname: Imai
authors.forename: Hidenori
authors.initials: H
authors.lastname: Karasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Furukawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Yoneda
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002336:Carnosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D015032:Zinc / Q000378:metabolism / Q000627:therapeutic use*; D017967:Zinc Compounds / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D009942:Organometallic Compounds; D017967:Zinc Compounds; D013853:Thioacetamide; C061957:polaprezinc; D002336:Carnosine; D015032:Zinc