Polaprezinc (Zinc L-Carnosine) Is a Potent Inducer of Anti-oxidative Stress Enzyme, Heme Oxygenase (HO)-1 — a New Mechanism of Gastric Mucosal Protection

• Published in: Journal of Pharmacological Sciences Vol. 110; no. 3; pp. 285 - 294
• Main Authors: Ueda, Kazuki, Ueyama, Takashi, Oka, Masashi, Ito, Takao, Tsuruo, Yoshihiro, Ichinose, Masao
• Format: Journal Article
• Language: English; Japanese
• Published: Japan Elsevier B.V 2009; The Japanese Pharmacological Society; Elsevier
• Subjects: Animals; Anti-Ulcer Agents - pharmacology; apoptosis; Apoptosis - drug effects; Carnosine - analogs & derivatives; Carnosine - pharmacology; Dose-Response Relationship, Drug; Enzyme Induction; gastric mucosa; Gastric Mucosa - drug effects; Gastric Mucosa - enzymology; heme oxygenase; Heme Oxygenase-1 - biosynthesis; HSP70 Heat-Shock Proteins - biosynthesis; Hydrochloric Acid - pharmacology; Male; Metalloporphyrins - pharmacology; mucosal protection; Organometallic Compounds - pharmacology; Oxidative Stress; Rats; Rats, Wistar; zinc compound; Zinc Compounds - pharmacology; heme oxygenase; gastric mucosa; zinc compound; apoptosis; mucosal protection
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.09056FP

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.