Studies on non-steroidal anti-inflammatory drugs-induced gastrointestinal damage: Participation in free radicals.

非甾体抗炎药所致胃肠道损伤的研究：自由基的参与。

• 批准号: 15590065
• 负责人: MIURA Toshiaki
• 金额: $ 2.24万
• 依托单位: Hokkaido Pharmaceutical University School of Pharmacy
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590065/
• 关键词: Non-steroidal anti-inflammatory drugs; gastrointestinal lesion; peroxidase; free radical; sulfhydryl group; lipid peroxidation; prostaglandin H synthase; cyclooxygenase; アスピリン; サリチル酸; ラクトペルオキシダーゼ; クレアチンキナーゼ; 胃粘膜; フリーラジカル; グルタチオンラジカル; 吸着; 抗

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammatory diseases, including rheumatoid arthritis and gout. The anti-inflammatory action of NSAIDs is due to the inhibition of prostaglandin synthesis by preventing cyclooxygenase (COX) activity of prostaglandin H synthase (PGS). However, administration of NSAIDs causes gastrointestinal mucosal lesions and a decrease in granulocytes as side effects. PGS catalyzes two distinct enzyme reactions: (1) bis-dioxygenation of arachidonic acid catalyzed by COX activity of PGS to form PGG_2; (2) reduction of the hydroperoxide group in PGG_2 by PGS hydroperoxidase. Most NSAID are oxidized by peroxidases to produce NSAID radicals that damage biological components, such as lipids and enzymes. Indomethacin, phenylbutazone and piroxicam are more toxic under aerobic conditions than anaerobic conditions during the interaction with peroxidase. We indicate the contribution of peroxidases in the formation of gastrointestinal mucosal lesions induced by NSAIDs.

非甾体类抗炎药（NSAIDs）广泛用于治疗炎症性疾病，包括类风湿性关节炎和痛风。NSAID的抗炎作用是由于通过阻止前列腺素H合酶（PGS）的环氧合酶（考克斯）活性来抑制前列腺素合成。然而，NSAID的给药引起胃肠道粘膜病变和粒细胞减少作为副作用。PGS催化两种不同的酶反应：（1）花生四烯酸在PGS的考克斯（COX）活性的催化下发生双氧化反应生成PGG_2;（2）PGS氢过氧化物酶（HPO）还原PGG_2中的氢过氧化物基团。大多数NSAID被过氧化物酶氧化以产生NSAID自由基，其破坏生物组分，如脂质和酶。吲哚美辛、保泰松和吡罗昔康在与过氧化物酶相互作用期间，在有氧条件下比在厌氧条件下毒性更大。我们指出过氧化物酶在非甾体抗炎药引起的胃肠道粘膜病变的形成中的作用。

项目成果

Inactivation of alphal-antiproteinase induced by phenylbutazone : participation of peroxyl radicals and hydroperoxide

保泰松诱导的α-抗蛋白酶失活：过氧自由基和氢过氧化物的参与

• 发表时间: 2006
• 期刊: Basic Clin Pharmacol Toxicol 99.3
• 作者: 三浦敏明;村岡早苗
• 通讯作者: 村岡早苗

村岡早苗, 三浦俊明: "Inactivation of creatine kinase during the interaction of mefenamic acid with horseradish peroxidase and hydrogen peroxide."Life Sciences. 72. 1897-1907 (2003)

Sanae Muraoka，Toshiaki Miura：“甲灭酸与辣根过氧化物酶和过氧化氢相互作用期间肌酸激酶失活。”生命科学 72。1897-1907 (2003)

Inhibition of xanthine oxidase by phytic acid and its antioxidative action

• DOI: 10.1016/j.lfs.2003.09.040
• 发表时间: 2004-02-13
• 期刊: LIFE SCIENCES
• 影响因子: 6.1
• 作者: Muraoka, S;Miura, T
• 通讯作者: Miura, T

ペルオキシダーゼによるNSAIDsの代謝 : 消化管粘膜障害との関連性

过氧化物酶对非甾体抗炎药的代谢：与胃肠道粘膜疾病的关系

• 发表时间: 2007
• 期刊: 薬学雑誌 127 (4)
• 作者: 三浦俊明;村岡早苗
• 通讯作者: 村岡早苗

Salicylic acid-induced inactivation of creaine Kinase in the presence of lactoperoxidase and H_2O_2

乳过氧化物酶和 H_2O_2 存在下水杨酸诱导的肌酸激酶失活

• 发表时间: 2005
• 期刊: Chemico-Biological Interactions 151
• 作者: 村岡早苗;三浦俊明
• 通讯作者: 三浦俊明