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

Journal of Pharmacological Sciences

Kazuki Ueda¹  Takao Ito²  Masao Ichinose¹  Yoshihiro Tsuruo²  Masashi Oka¹  Takashi Ueyama² 

[1] 2nd Department of Internal Medicine, Wakayama Medical University, Japan;Department of Anatomy and Cell Biology, Wakayama Medical University, Japan

关键词: heme oxygenase;    mucosal protection;    zinc compound;    apoptosis;    gastric mucosa;   

DOI  :  10.1254/jphs.09056FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(39)Cited-By(17)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.

【 授权许可】

Unknown