title: Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats.
abstract: 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.
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Chengli
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Song
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Gu
authors.initials: G
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Youfu
authors.initials: Y
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: ping.cheng@foxmail.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: zhengyu_iris@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006635:Histamine H2 Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D007052:Ibuprofen / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006635:Histamine H2 Antagonists; D007052:Ibuprofen
keywords: Antioxidant enzymes; Gastric ulcer index; Histamine-2 receptor antagonists; Ibuprofen; Lipid peroxidation