title: Zinc L-carnosine protects against mucosal injury in portal hypertensive gastropathy through induction of heat shock protein 72.
abstract: OBJECTIVE
  Increased susceptibility to gastric mucosal injury is observed in portal hypertensive gastropathy (PHG). In this study, the effects of zinc L-carnosine, an anti-ulcer drug, were evaluated on expression of heat shock protein (hsp) 72 and cytoprotection in gastric mucosa in a rat model of PHG.
  
  
  METHODS
  Portal hypertensive gastropathy with liver cirrhosis was induced by bile duct ligation for 4 weeks in male Sprague-Dawley rats. Expression of gastric mucosal hsp72 was evaluated by Western blotting at 6 h after intragastric administration of L-carnosine, zinc sulfate, or zinc L-carnosine. Blood was also collected for determination of serum zinc level. Mucosal protective abilities against hydrochloric acid (HCl) (0.6N) followed by pretreatment with L-carnosine, zinc sulfate or zinc L-carnosine were also studied.
  
  
  RESULTS
  L-carnosine, zinc sulfate, and zinc L-carnosine induced hsp72 in gastric mucosa of rats with bile duct ligation. Zinc sulfate and zinc L-carnosine suppressed HCl-induced mucosal injury. However, L-carnosine could not suppress HCl-induced mucosal injury. Serum zinc levels were significantly elevated after zinc L-carnosine administration. Furthermore, pretreatment with zinc L-carnosine (30-300 mg/kg) increased the expression of hsp72 in gastric mucosa and prevented HCl-induced mucosal injury in rats with bile duct ligation in a dose-dependent manner.
  
  
  CONCLUSIONS
  Zinc derivatives, especially zinc L-carnosine, protected portal hypertensive gastric mucosa with increased hsp72 expression in cirrhotic rats. It is postulated that zinc L-carnosine may be beneficial to the mucosal protection in PHG as a 'chaperone inducer'.
authors.affiliation: Department of Gastroenterology, Akita University School of Medicine, Akita, Japan.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Mikami
authors.forename: Michiro
authors.initials: M
authors.lastname: Otaka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Goto
authors.forename: Ayako
authors.initials: A
authors.lastname: Endoh
authors.forename: Kouichi
authors.initials: K
authors.lastname: Miura
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Ohshima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yoneyama
authors.forename: Michiko
authors.initials: M
authors.lastname: Sato
authors.forename: Tomomi
authors.initials: T
authors.lastname: Shibuya
authors.forename: Daisuke
authors.initials: D
authors.lastname: Segawa
authors.forename: Ei
authors.initials: E
authors.lastname: Kataoka
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Yoshino
authors.forename: Satoko
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Wataru
authors.initials: W
authors.lastname: Sato
authors.forename: Masaru
authors.initials: M
authors.lastname: Odashima
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D015153:Blotting, Western; D002336:Carnosine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D006975:Hypertension, Portal / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D019287:Zinc Sulfate / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
chemical_list: D050884:HSP72 Heat-Shock Proteins; D019287:Zinc Sulfate; D002336:Carnosine