Gastroprotective effects of several H₂RAs on ibuprofen-induced gastric ulcer in rats

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• 作者：Jing Liu¹ ; Dan Sun¹ ; Jinfeng He¹ ; Chengli Yang ; Tingting Hu ; Lijing Zhang ; Hua Cao ; Ai-ping Tong ; Xiangrong Song ; Yongmei Xie ; Gu He ; Gang Guo ; Youfu Luo ; Ping Cheng ; ^{ping.cheng@foxmail.com" class="auth_mail" title="E-mail the corresponding author} ; Yu Zheng ; ^{zhengyu_iris@163.com" class="auth_mail" title="E-mail the corresponding author} ; ^{zhengyu82@scu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Ibuprofen ; Histamine-2 receptor antagonists ; Gastric ulcer index ; Lipid peroxidation ; Antioxidant enzymes
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 March 2016
• 年：2016
• 卷：149
• 期：Complete
• 页码：65-71
• 全文大小：1677 K

文摘

Ibuprofen is the first line of treatment for osteoarthritis and arthritis. The main side effects of ibuprofen especially in long-term treatment include gastric ulcer, duodenal ulcer and indigestion etc. Therefore, screening drugs with effective gastric protective effects and low toxicity for combination therapy with ibuprofen is necessary. The mechanism of gastric damage induced by ibuprofen is still unclear, however, cell damage caused by reactive oxygen species (ROS) is considered as the main reason. Preliminary screening of literature with the criteria of low toxicity led to four histamine-2 receptor antagonists (H₂RAs): nizatidine, famotidine, lafutidine, and roxatidine acetate, which were selected for further investigation. These drugs were evaluated systemically by examining the gastric ulcer index, lipid peroxidation (LPO), membrane permeability, toxicity to main organs, and the influence on the activity of antioxidant enzymes, and myeloperoxidase (MPO). Nizatidine was found to be the best gastric protective agent. It exhibited excellent protective effect by increasing antioxidant enzyme activity, decreasing MPO activity, reducing LPO, and membrane permeability. Combination treatment with nizatidine and ibuprofen did not show any significant toxicity. Nizatidine was considered as a good option for combination therapy with ibuprofen especially for diseases that require long-term treatment such as arthritis and osteoarthritis.