Involvement of reactive oxygen species and nitric oxide in gastric ischemia-reperfusion injury in rats: protective effect of tetrahydrobiopterin.
The purpose of this study was to examine whether tetrahydrobiopterin (BH4), a cofactor of nitric oxide (NO) synthase, attenuates gastric ischemia-reperfusion injury induced by clamping of the celiac artery. Gastric injury was assessed by a formation of gastric mucosal erosions. The gastric injury was observed at 30 and 60 min after reperfusion following 30-min ischemia and was reduced by superoxide dismutase (SOD), catalase, or NO synthase inhibitors. Therefore, reactive oxygen species (ROS) and NO seem to be implicated in the ischemia-reperfusion injury. Treatment with BH4 reduced the ischemia-reperfusion injury. Pretreatment with sepiapterin, a precursor of BH4, also reduced the ischemia-reperfusion injury with an increase in BH4 content in serum and stomach. Both the increase in BH4 content and the protective effect of sepiapterin were prevented of pretreatment with N-acetylserotonin, an inhibitor of BH4 synthesis. These results suggest that the increase in BH4 content may protect against gastric ischemia-reperfusion injury via reduction of ROS and/or NO toxicity. BH4 might be useful as a therapeutic agent for gastric ischemia-reperfusion injury.
Ishii
M
M
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Shimizu
S
S
Nawata
S
S
Kiuchi
Y
Y
Yamamoto
T
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D011621:Pteridines / Q000494:pharmacology; D011622:Pterins; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000517:prevention & control*; D013270:Stomach / Q000098:blood supply*
D000975:Antioxidants; D011621:Pteridines; D011622:Pterins; D017382:Reactive Oxygen Species; D001708:Biopterins; D009569:Nitric Oxide; C016727:sepiapterin; C003402:sapropterin