Shigenobu Ueda

Kyoto Prefectural University of Medicine

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Motoharu Kondo

Kyoto Prefectural University of Medicine

Yuji Naito

Shizuoka Medical Center

Hajime Oyamada

Akita University

Takeo Yoshikawa

RIKEN Center for Brain Science

S Sugino

Kyoto Prefectural University of Medicine

T Takemura

Sumitomo Dainippon Pharma (Japan)

Tetsuya Tanigawa

Osaka City University

Shigeru Sugino

Kyoto Prefectural University of Medicine

Hirokazu Oyamada

Matsushita Memorial Hospital

Toshikazu Yoshikawa

Kyoto Prefectural University of Medicine

Cooperative Institutions

Kyoto Prefectural University of Medicine

Osaka University

Kyoto University

Matsushita Memorial Hospital

Kyoto City Hospital

Hiroshima University

Kobe Central Hospital

Aichi Medical University

Memorial Hospital of South Bend

Kyoto Prefectural University

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Effect of Zinc-Carnosine Chelate Compound (Z-103), A Novel Antioxidant, on Acute Gastric Mucosal Injury Induced by Ischemia-Reperfusion in Rats

Free Radical Research Communications (1991)

Takeo Yoshikawa Yuji Naito Tohru Tanigawa T. Yoneta Mitsunori Yasuda

The protective effect of a novel synthetic zinc-carnosine chelate compound, zinc N-(3-aminopropionyl)-L-histidine (Z-103), on the gastric mucosal injury induced by ischemia-reperfusion was studied in rats. Ischemia and reperfusion injury was produced on the rat stomach by applying a small clamp to the celiac artery for 30 min and by removal of the clamp for 30 min. The decrease in the gastric mucosal blood flow was not influenced by the treatment with Z-103. The increase in total area of the erosions on the stomach after ischemia-reperfusion and the increase in lipid peroxides in the gastric mucosa were significantly inhibited by the oral administration of Z-103. In addition, Z-103 inhibited lipid peroxidation of rat brain homogenate and liver microsome in vitro. These results suggest that the protective effect of Z-103 against the aggravation of gastric mucosal injury induced by ischemia-reperfusion may be due to its inhibitory effect on lipid peroxidation.

Carnosine

10.3109/10715769109088958

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Citations (77)

Detection of superoxide radicals from alveolar macrophages by electron spin resonance and chemiluminescence and the effects of endotoxin.

Japanese Journal of Clinical Immunology (1990)

Toshikazu Yoshikawa Shigenobu Ueda Mitsunori Yasuda Hiroshi Ichikawa Syuji Takahashi

活性酸素は成人呼吸窮迫症候群などの肺胞障害の成因と関連があると考えられ,好中球からの活性酸素がARDSで亢進することが知られている.マクロファージは免疫効果を有する物質,化学因子や活性酸素などを放出して,肺の防御に重要な役割を有している.エンドトキシンの刺激により肺胞マクロファージはこれらを放出するが,肺の組織障害の一因であるとも考えられる.今回われわれは肺胞マクロファージ由来のスーパーオキシドDMPOを用いたESR-スピントラップ法およびMCLAを用いた化学発光法で検出し,さらにエンドトキシンの肺胞マクロファージのスーパーオキシド産生への影響について検討した.肺胞マクロファージ由来のスーパーオキシドは,刺激剤にPMAを使い, DMPOを用いたESR-スピントラップ法およびMCLAを用いた化学発光法で検出が可能であった.エンドトキシンの影響は動物にエンドトキシンを投与した場合でも,直接エンドトキシンを細胞浮遊液に添加した場合も, PMA刺激により対照群と比較しスーパーオキシドの産生が亢進した.肺胞マクロファージからの〓産生は,エンドトキシンの有無にかかわらずPMA非添加時には認められなかった.また,エンドトキシンの投与により肺胞洗浄液中の総蛋白,アルブミンおよびアンギオテンシンI変換酵素の漏出の有意な増加を認めた.以上より,肺胞マクロファージの〓産生能に対するエンドトキシンの効果は,肺胞マクロファージが何らかの刺激を受けた場合に,その産生能をより強く亢進させる効果であり,エンドトキシンによる肺障害と肺胞マクロファージ由来の〓と何らかの関係があるものと考えられた.

10.2177/jsci.13.544

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[Role of free radicals and lipid peroxidation in gastric mucosal injury induced by ischemia-reperfusion in rats].

PubMed (1990)

Takeo Yoshikawa Shigenobu Ueda S Takahashi Yuji Naito Hajime Oyamada

Ischemia and reperfusion is of the greatest importance in the pathology of various diseases. This study was designed to investigate the role of oxygen-derived free radicals and lipid peroxidation in gastric mucosal injury induced by ischemia-reperfusion in rats. Clamping of the celiac artery in rats reduced the gastric mucosal blood flow to 10% of that measured before the clamping. Gastric mucosal injury, such as spotty and linear hemorrhagic erosions, was seen in rats 60 min of the reperfusion following 30 min of ischemia. Thiobarbituric acid (TBA) reactants in the gastric mucosa were increased after the reperfusion. The increase in gastric mucosal lesions and TBA reactants were significantly inhibited by the treatment with SOD+ catalase and allopurinol. These results suggest that oxygen-derived free radicals and lipid peroxidation may play an important role in the pathogenesis of acute gastric mucosal lesions induced by ischemia-reperfusion.

Thiobarbituric acid

Pathogenesis

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Relationship between esophageal candidiasis and histamine H2-receptor antagonists.

Nihon Naika Gakkai Zasshi (1988)

Hirokazu Oyamada Toshikazu Yoshikawa Yuji Naito Shigenobu Ueda Toshiki Takemura

ヒスタミンH2受容体拮抗薬による胃内の低酸状態と食道カンジダ症の関連を検討した.免疫能の正常な42例の胃液中のCandida albicans検出率は,胃液pHが5以上で57.1%と, pH3以下の20.0%に比べ有意に高く,また,ヒスタミンH2受容体拮抗薬投与群のCandida albicans検出率は63.2%と非投与群の21.7%に比べ有意に高かった.すなわち,本薬の胃酸分泌抑制作用は胃内のCandida albicansの発育を助長すると考えられた.また,血液悪性疾患51例の検討では,本薬投与群の41.4%に食道カンジダ症を合併し,非投与群の22.7%に比べ有意に高く,免疫能の低下した症例に対する本薬の投与は食道カンジダ症を誘発する危険があると示唆された.

Esophageal candidiasis

10.2169/naika.77.1546

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Citations (1)

Augmentative effects of tumor necrosis factor-alpha (human, natural type) on polymorphonuclear leukocyte-derived superoxide generation induced by various stimulants

International Journal of Immunopharmacology (1992)

Toshikazu Yoshikawa Hirohisa Takano Yuji Naito Hirokazu Oyamada Shigenobu Ueda

Zymosan

Phorbol

10.1016/0192-0561(92)90010-i

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Citations (31)

Protective effect of cilostazol, an antiplatelet drug, on experimental disseminated intravascular coagulation syndrome.

Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics (1988)

Shigenobu Ueda

Cilostazol

Antiplatelet drug

10.3999/jscpt.19.317

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Role of Xanthine-Xanthine Oxidase Systems and Polymorphonuclear Leukocytes in Lipid Peroxidation in Compound 48/80-Induced Gastric Mucosal Injury in Rats

Advances in experimental medicine and biology (1990)

Toshiki Takemura Toshikazu Yoshikawa Yuji Naito Shigenobu Ueda Toru Tanigawa

Xanthine

Compound 48/80

Pathogenesis

10.1007/978-1-4684-5730-8_66

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Citations (7)

[Role of active oxygen species and lipid peroxidation in liver injury induced by ischemia-reperfusion].

PubMed (1990)

Takeo Yoshikawa Hajime Oyamada Haruyo Ichikawa Yoshiko Naito Shigenobu Ueda

The role of superoxide and lipid peroxidation in liver injury induced by ischemia-reperfusion was investigated in rats. Ischemic condition of the liver was created by applying small clamps to the right branch of portal vein and the right hepatic artery for 15 min. Clamping of hepatic artery and portal vein could decrease the hepatic blood flow to about 30% of that measured before the clamping. Levels of serum GPT and thiobarbituric acid (TBA) reactive substances in the liver tissue were significantly increased 30 min after the reperfusion following 15 min of ischemia. The increase in serum GPT and TBA reactants in the liver tissue was significantly inhibited by the treatment with superoxide dismutase combined with catalase. The treatment with allopurinol significantly inhibited the elevation of serum GPT levels and showed a tendency to inhibit the increase in TBA reactants in liver tissue. These results suggest that active oxygen species and lipid peroxidation may play an important role in the pathogenesis of ischemia-reperfusion injury in the liver, and hypoxanthine-xanthine oxidase system may be one of the main sources of active oxygen species.

Thiobarbituric acid

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Effect of seleno-organic compound (Ebselen) on acute gastric mucosal lesion.

Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics (1989)

Shigenobu Ueda

Ebselen

10.3999/jscpt.20.99

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Citations (0)

Ischemia-Reperfusion Injury and Free Radical Involvement in Gastric Mucosal Disorders