Polaprezinc (Zinc L-carnosine) is a potent inducer of anti-oxidative stress enzyme, heme oxygenase (HO)-1 - a new mechanism of gastric mucosal protection.
Heme oxygenase (HO)-1 is implicated in cytoprotection in various organs. We tested a possibility that polaprezinc (PZ), an anti-ulcer drug, could induce HO-1 in the gastric mucosa. Male 6-week-old Wistar rats were intragastrically administered PZ. Gastric expression of HO-1 was assessed by real time RT-PCR and western blotting, and localization of HO-1 was observed by in situ hybridization and immunohistochemistry. The levels of HO-1 mRNA were increased in a dose-dependent manner. The levels of HO-1 mRNA were increased 4-fold by PZ at the dose of 200 mg/kg at 3 h as compared with control levels. The levels of immunoreactive HO-1 were increased 3-fold at 6 h. Signals for HO-1 mRNA and immunoreactivity were detected strongly in the surface gastric mucosal cells and moderately in the gastric macrophages. Treatment with an HO-1 inhibitor, stannous mesoporphyrin (SnMP) significantly worsened the HCl-induced acute gastric mucosal lesions and increased the apoptosis of mucosal cells. Mucosal lesions were decreased by pretreatment with PZ, while they were increased by co-administration with SnMP. These data indicate for the first time that PZ is an effective inducer of HO-1 in the stomach. PZ-induced HO-1 functions as a part of the mucosal protective effects of PZ.
Ueda
Kazuki
K
2nd Department of Internal Medicine, Wakayama Medical University, Japan.
Ueyama
Takashi
T
Oka
Masashi
M
Ito
Takao
T
Tsuruo
Yoshihiro
Y
Ichinose
Masao
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006851:Hydrochloric Acid / Q000494:pharmacology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017967:Zinc Compounds / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D018840:HSP70 Heat-Shock Proteins; D008665:Metalloporphyrins; D009942:Organometallic Compounds; D017967:Zinc Compounds; C518404:stannous mesoporphyrin; C061957:polaprezinc; D002336:Carnosine; D051547:Heme Oxygenase-1; D006851:Hydrochloric Acid