Zinc L-carnosine protects against mucosal injury in portal hypertensive gastropathy through induction of heat shock protein 72.
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'.
Mikami
Ken-ichiro
K
Department of Gastroenterology, Akita University School of Medicine, Akita, Japan.
Otaka
Michiro
M
Watanabe
Daisuke
D
Goto
Takashi
T
Endoh
Ayako
A
Miura
Kouichi
K
Ohshima
Shigetoshi
S
Yoneyama
Kazuo
K
Sato
Michiko
M
Shibuya
Tomomi
T
Segawa
Daisuke
D
Kataoka
Ei
E
Yoshino
Ryutaro
R
Takeuchi
Satoko
S
Sato
Wataru
W
Odashima
Masaru
M
Watanabe
Sumio
S
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*
D050884:HSP72 Heat-Shock Proteins; D019287:Zinc Sulfate; D002336:Carnosine