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Involvement of Reactive Oxygen Species and Nitric Oxide in Gastric Ischemia-Reperfusion Injury in Rats

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Abstract

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.

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REFERENCES

  1. Rubanti GM: Vascular effects of oxygen-derived free radicals. Free Radic Biol Med 4:107-120, 1988

    PubMed  Google Scholar 

  2. Granger DN: Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. Am J Physiol 255:H1269-H1275, 1988

    PubMed  Google Scholar 

  3. Smith SM, Grisham MB, Manci EA, Granger DN, Russell JM: Gastric mucosal injury in the rat: Role of iron and xanthine oxidase. Gastroenterology 92:950-956, 1987

    PubMed  Google Scholar 

  4. Yoshikawa T, Ueda S, Naito Y, Takahashi S, Oyamada H, Morita Y, Yoneta T, Kondo M: Role of oxygen-derived free radicals in gastric mucosal injury induced by ischemia or ischemia-reperfusion in rats. Free Radic Res Commun 7:3-6, 1989

    Google Scholar 

  5. Sonoda M, Asakuno G, Matsuki M, Satomi A, Ishida K, Sakagishi Y: Radical trapping by PBN during reperfusion in rabbit gastric mucosa. Free Radic Res Commun 19:S185-S191, 1993

    PubMed  Google Scholar 

  6. Wada K, Kamisaki Y, Ohkura T, Kanda G, Nakamoto K, Kishimoto Y, Ashida K, Itoh T: Direct measurement of nitric oxide release in gastric mucosa during ischemia-reperfusion in rats. Am J Physiol 274:G465-G471, 1998

    PubMed  Google Scholar 

  7. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA: Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620-1624, 1990

    PubMed  Google Scholar 

  8. Noronha-Dutra AA, Epperlein MM, Woolf N: Reaction of nitric oxide with hydrogen peroxide to produce potentially cytotoxic singlet oxygen as a model for nitric oxide-mediated killing. FEBS Lett 321:59-62, 1993

    Article  PubMed  Google Scholar 

  9. Radi R, Beckman JS, Bush KM, Freeman BA: Peroxynitriteinduced membrane lipid peroxidation: The cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 288:481-487, 1991

    PubMed  Google Scholar 

  10. Patel VC, Yellon DM, Singh KJ, Neild GH, Woolfson RG: Inhibition of nitric oxide limits infarct size in the in situ rabbit heart. Biochem Biophys Res Commun 194:234-238, 1993

    PubMed  Google Scholar 

  11. Ischiropoulos H, Al-Mehdi AB, Fisher AB: Reactive species in ischemic rat lung injury: Contribution of peroxynitrite. Am J Physiol 269:L158-L164, 1995

    PubMed  Google Scholar 

  12. Yasmin W, Strynadka KD, Schulz R: Generation of peroxynitrite contributes to ischemia-reperfusion injury in isolated rat hearts. Cardiovas Res 33:422-432, 1997

    Google Scholar 

  13. Andrews FJ, Malcontenti-Wilson C, O'Brien PE: Protection against gastric ischemia-reperfusion injury by nitric oxide generators. Dig Dis Sci 39:366-373, 1994

    PubMed  Google Scholar 

  14. Ishii M, Shimizu S, Yamamoto T, Momose K, Kuroiwa Y: Acceleration of oxidative stress-induced endothelial cell death by nitric oxide synthase dysfunction accompanied with decrease in tetrahydrobiopterin content. Life Sci 61:739-747, 1997

    PubMed  Google Scholar 

  15. Ishii M, Shimizu S, Momose K, Yamamoto T: Reduction by tetrahydrobiopterin of H2O2-induced endothelial cell injury. Pharmacol Toxicol 82:280-286, 1998

    PubMed  Google Scholar 

  16. Shimizu S, Ishii M, Momose K, Yamamoto T: Role of tetrahydrobiopterin in the function of nitric oxide synthase, and its cytoprotective effect. Int J Mol Med 2:533-540, 1998

    PubMed  Google Scholar 

  17. Shimizu S, Ishii M, Kawakami Y, Momose K, Yamamoto T: Protective effects of tetrahydrobiopterin against nitric oxide-induced endothelial cell death. Life Sci 63:1585-1592, 1998

    PubMed  Google Scholar 

  18. Ishii M, Shimizu S, Momose K, Yamamoto T: SIN-1-induced cytotoxicity in cultured endothelial cells involves reactive oxygen species and nitric oxide: Protective effect of sepiapterin. J Cardiovasc Pharmacol 33:295-300, 1999

    PubMed  Google Scholar 

  19. Kojima S, Nimura K, Komatsu H, Taguchi T, Iizuka H: Modulation of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) induced HL-60 cell death by tetrahydrobiopterin. Anticancer Res 17:929-938, 1997

    PubMed  Google Scholar 

  20. Fukushima T, Nixon JC: Analysis of reduced forms of biopterin in biological tissues and fluids. Anal Biochem 102:176-188, 1980

    PubMed  Google Scholar 

  21. Lamarque D, Whittle BJR: Involvement of superoxide and xanthine oxidase in neutrophil-independent rat gastric damage induced by NO donors. Br J Pharmacol 116:1843-1848, 1995

    PubMed  Google Scholar 

  22. Hata Y, Ota S, Hiraishi H, Terano A, Ivey KJ: Nitric oxide enhances cytotoxicity of cultured rabbit gastric mucosal cells induced by hydrogen peroxide. Biochim Biophys Acta 1290:257-260, 1996

    PubMed  Google Scholar 

  23. Shen R-S, Zhang Y: Antioxidation activity of tetrahydrobiopterin in pheochromocytoma PC 12 cells. Chem Biol Interactions 78:307-319, 1991

    Google Scholar 

  24. Kojima S, Icho T, Kajiwara Y, Kubota K: Neopterin as an endogenous antioxidant. FEBS Lett 304:163-166, 1992

    PubMed  Google Scholar 

  25. Icho T, Kojima S, Hayashi M, Kajiwara Y, Kitabatake K, Kubota K: Suppression of ischemia-reperfusion injury in murine models by neopterins. Toxicol Appl Pharmacol 130:27-31, 1995

    PubMed  Google Scholar 

  26. Kojima S, Ona S, Iizuka I, Arai T, Mori H, Kubota K: Antioxidative activity of 5,6,7,8,-tetrahydrobiopterin and its inhibitory effect on paraquat-induced cell toxicity in cultured rat hepatocytes. Free Radic Res 23:419-430, 1995

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Clinical Pharmacy and Pathophysiology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Masakazu Ishii, Shunichi Shimizu, Shuichi Nawata, Yuji Kiuchi & Toshinori Yamamoto

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  1. Masakazu Ishii
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  2. Shunichi Shimizu
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  3. Shuichi Nawata
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  4. Yuji Kiuchi
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  5. Toshinori Yamamoto
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Ishii, M., Shimizu, S., Nawata, S. et al. Involvement of Reactive Oxygen Species and Nitric Oxide in Gastric Ischemia-Reperfusion Injury in Rats. Dig Dis Sci 45, 93–98 (2000). https://doi.org/10.1023/A:1005413511320

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