Effects of sucralfate, cimetidine and rabeprazole on mucosal hydroxyproline content in healing of ethanol-hcl-induced gastric lesions.
1. No general consensus has been reached on the treatment of acute gastric lesions. The aims of the present study were to clarify the effects of sucralfate, cimetidine and rabeprazole monotherapies and combination therapies on acute gastric lesions from the viewpoint of connective tissue regeneration. 2. Gastric lesions were experimentally created by the oral administration of 50% ethanol-0.15 mol/L HCl to rats. After 30 min, the anti-ulcer agents sucralfate (100 mg/kg), cimetidine (20 mg/kg) and rabeprazole (2 mg/kg) were administered separately or in combination and the stomach was excised at different times to measure the level of hydroxyproline in the gastric mucosa and determine lesion index. Immunostaining against prolylhydroxylase was performed on some specimens. 3. In the control group, lesion index decreased linearly from 30 min after ethanol-HCl administration and the level of mucosal hydroxyproline peaked between 2 and 4 h later. Although sucralfate significantly promoted lesion healing, it had no effect on mucosal hydroxyproline level. Cimetidine suppressed increases in mucosal hydroxyproline and prolonged lesion healing, but these findings were reversed by combining cimetidine and sucralfate. Rabeprazole had no significant effect on lesion healing, but promoted lesion healing in combination with sucralfate. Immunohistochemical analysis showed that prolylhydroxylase was expressed in spindle cells that lined the glandular cells in a boundary area between normal and injured tissues. 4. Under conditions in which the effects of intragastric pH are minimal, sucralfate is superior to antisecretory agents in promoting the healing of acute gastric lesions.
Arisawa
Tomiyasu
T
Department of Gatroenterology, Fujita Health University, School of Medicine, Kutsukake-cho, Toyoake, Japan. tarisawa@fujita-hu.ac.jp
Shibata
Tomoyuki
T
Kamiya
Yoshio
Y
Nagasaka
Mitsuo
M
Nakamura
Masakatsu
M
Fujita
Hiroshi
H
Hasegawa
Shin
S
Harata
Masao
M
Nakamura
Masahiko
M
Mizuno
Tamaki
T
Tahara
Tomomitsu
T
Ohta
Yoshiji
Y
Nakano
Hiroshi
H
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002927:Cimetidine / Q000494:pharmacology* / Q000627:therapeutic use; D000431:Ethanol / Q000008:administration & dosage; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006851:Hydrochloric Acid / Q000008:administration & dosage; D006909:Hydroxyproline / Q000378:metabolism*; D008297:Male; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D064750:Rabeprazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013392:Sucralfate / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D064750:Rabeprazole; D000431:Ethanol; D013392:Sucralfate; D002927:Cimetidine; D011393:Procollagen-Proline Dioxygenase; D006851:Hydrochloric Acid; D006909:Hydroxyproline