Comparison of the Effects of Pantoprazole Enantiomers on Gastric Mucosal Lesions and Gastric Epithelial Cells in Rats

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概要

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• (±)-Pantoprazole sodium, [(±)-PAN・Na], is a proton pump inhibitor that is administered as a racemate. The protective effects of (-)-PAN・Na, (+)-PAN・Na and (±)-PAN・Na on various experimental ulcers in animals were compared. (-)-PAN・Na inhibited gastric lesions induced by water-immersion stress, aspirin, ethanol, and reserpine in adose-dependentmanner. The dosethatinhibited 50% of lesions (ID_50) were 2.72 ± 1.03, 1.60 ± 0.64. 4.12 ± 2.18, and 2.77 ± 0.86 mg/kg, respectively. The ID_50 values of(+)-PAN・Na and (±)-PAN-Na were 1.7, 2.6, 1.8, 2.7 and 1.5, 1.7, 1.6, 1.9 times higher, respectively, than that of (-)-PAN・Na. Primary culture of rat gastric epithelial cells was investigated as an in vitro model for comparing the cell protective effects among the three agents. Exposed to the three drugs at the concentrations of 2.5 × 10^<-1>-2.5 × 10^<-5> mg/ml, cultured cells were treated with either pH 3.5 medium or 3.5 mM indomethacin. Cytoprotection was evaluated by MTT. (-)-PAN・Na, (+)-PAN・Na and (±)-PAN・Na provided significant cytoprotective effects when the cells were pretreated with the drugs prior to exposure to 3.5 mM indomethacin, whereas, when they were treated concurrently, no significant cytoprotective effects were found. In pH 3.5 medium-induced damage, the three drugs had marked protective effects on gastric cells, however, when the concentration of drugs was high (0.25 mg/ml), only (+)-PAN・Na had significant cytoprotection. We concluded that the cytoprotective mechanisms of (-)-PAN・Na and (+)-PAN・Na are different. The results of in vitro experiments were not in complete accordance with the in vivo results, suggesting that the effects of the three drugs on ulcer inhibition are mainly due to the effects of acid inhibition rather than cytoprotection.

• 公益社団法人日本薬学会の論文
• 2004-02-01

著者

• Wang Minwei

  Department Of Pharmacology Shenyang Pharmaceutical University

• CAO Hong

  Department of Chemistry, Faculty of Science, Hiroshima University

• Cao Hong

  中華人民共和国

• Cao Hong

  Department Of Chemistry Faculty Of Science Hiroshima University

• Cheng Maosheng

  Department Of Pharmaceutical Engineering Shenyang Pharmaceutical University

• Jia Jianhui

  Department of Pharmacology, Shenyang Pharmaceutical University

• Wang Qinghe

  Department of Pharmaceutical Engineering, Shenyang Pharmaceutical University

• Jia Jianhui

  Department Of Pharmacology Shenyang Pharmaceutical University

• Wang Qinghe

  Department Of Pharmaceutical Engineering Shenyang Pharmaceutical University

• Wang Minwei

  Department Of Pharmacology School Of Life Science And Biopharmaceutics Shenyang Pharmaceutical Unive

• Cao Hong

  Department of Cardiology, Renmin Hospital of Wuhan University, China

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