Suppression of ischemia-reperfusion injury in murine models by neopterins.
We investigated the effects of D-neopterin (NP) and its reduced form, 5,6,7,8-tetrahydro-D-neopterin (NPH4), in two models of ischemia-reperfusion injury, i.e., ischemic paw edema in mice and gastric ischemia in rats. In ischemic paw edema, iv administration of either NP or NPH4 more potently inhibited the increase of paw thickness after release from ischemia than did administration of superoxide dismutase plus catalase or allopurinol. In gastric ischemia, NP and NPH4 also significantly suppressed the formation of gastric mucosal erosions. Lipid peroxidation in the stomach was increased by ischemia-reperfusion treatment, and the increase was inhibited by the administration of NP or NPH4. The minimum dose of NPH4 required to suppress the gastric ischemic injury in this experiment was 0.3 mg/kg of body weight. These results suggest that neopterin may be effective as a protective agent against ischemia-reperfusion injury, in which active oxygen species are believed to play a major role.
Central Research Laboratory, Asahi Breweries, Limited, Tokyo, Japan.
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Icho
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Kojima
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Hayashi
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Kajiwara
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Kitabatake
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Kubota
D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002374:Catalase / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D019798:Neopterin; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000627:therapeutic use
D017382:Reactive Oxygen Species; D001708:Biopterins; C023455:tetrahydroneopterin; D000493:Allopurinol; D019798:Neopterin; D002374:Catalase; D013482:Superoxide Dismutase