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Effects of activated granulocytes and O 2 on microcirculatory injury in acute gastric mucosal lesion in rats induced by sodium cinchophen

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Abstract

The contribution of granulocytes and their byproducts to acute gastric mucosal lesion (AGML) is unclear. Our previous study showed that granulocytes produced O 2 in the gastric mucosa of rats treated with 300 mg/kg of cinchophen (cinchophen ulcer, CU) and in rats subjected to 30 min-ischemia-reperfusion (IR). The present study investigated the effects of granulocytes and O 2 on microcirculatory injury (MCI) in the gastric mucosa in both models. To evaluate MCI, we measured the amount of extravasated Evans blue, and monitored changes in blood flow and the formation of vascular casts in the gastric mucosa of rats with and without leukopenia. Mucosal levels of interleukin-8 (IL-8) were also measured, to determine granulocyte migration into the stomach. Our findings were: (1) IL-8 was decreased 30–45 min after CU injection (C−I) or after the start of occlusion (S−O), and levels had increased 90 min after either treatment. (2) Evans blue increased 120–150 min after C−I or S−O. These increases were lower in leukopenic than in non-leukopenic rats. (3) The blood flow decreased after C−I or reperfusion and continued at the same level during the 180-min measurement period. in CU leukopenic rats, the blood flow decreased slowly and was restored gradually. In IR leukopenic rats, the blood flow did not decrease. (4) There was a partial lack of capillary network, narrowing of capillaries, and extravasation of resin 90–120 min after C−I and S−O, and the disturbances were reduced in leukopenic rats in both models. (5) The extravasation of resin was reduced by the administration of superoxide dismutase (SOD) at the time O 2 from granulocytes was being produced. (6) These reductions in the extravasation of resin due to leukopenia or SOD were smaller in CU than in IR rats. These findings indicate that granulocytes and O 2 contribute to some extent to the MCI in CU rats.

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References

  1. Smith SM, Holm-Rutili L, Perry M, et al. Role of neutrophils in hemorrhagic shock-induced gastric mucosal injury in the rat. Gastroenterology 1987;93:466–471.

    CAS  PubMed  Google Scholar 

  2. Harlan JM, Winn RK, Vedder NB, et al. In vivo models of leukocyte adherence to endothelium. In: Harlan JM, Liu DY (eds) Adhesion: Its role in inflammatory disease. New York: WH Freeman, 1992;117–150.

    Google Scholar 

  3. Nagamachi Y, Nishida Y, Akiyama N. Are epinephrine and gastrin accelerative factors of acute cinchophen ulcer?: Studies on gastric mucosal microcirculation and gastric secretion. Gastroenterol Jpn 1979;14:95–102.

    CAS  PubMed  Google Scholar 

  4. Tsuchiya M, Oda M, Nakamura M, et al. Studies of the autonomic nervous regulation of the gastric mucosal microcirculation in rats: With special reference to the pathogenesis of the experimental restraint-induced gastric ulcer (in Japanese with English abstract). Nippon Shokakibyo Gakkai Zasshi (Jpn J Gastroenterol) 1981, 78:1000–1014.

    CAS  PubMed  Google Scholar 

  5. Kitajima M, Shimizu A, Torii H, et al. Gastric microcirculatory change and development of acute gastric mucosal lesions (stress ulcer). Acta Physiol Hung 1989;73:137–148.

    CAS  PubMed  Google Scholar 

  6. Nagamachi Y. New method of obtaining cinchophen ulcer in dogs. Am J Dig Dis 1977;22:761–768.

    Article  CAS  PubMed  Google Scholar 

  7. Takahashi T, Nagamachi Y. Observation of O 2 generation in in situ gastric mucosa of rats in the development of experimental acute gastric mucosal lesions. Current Clinical Practice Series 65. Tokyo: Excerpta Medica, 1992:260–266.

    Google Scholar 

  8. Takahashi A. Effects of superoxide anion and granulocytes on in situ gastric mucosa of rat in the development of experimental acute gastric mucosal lesions (in Japanese with English abstract). Nippon Shokakibyo Gakkai Zasshi (Jpn J Gastroenterol) 1993;90:1623–1632.

    CAS  PubMed  Google Scholar 

  9. Takahashi A, Nakano M, Nagamachi Y, et al. Detection of O 2 generated in the rat gastric mucosa in situ during reperfusion following ischemia. J Clin Biochem Nutr 1994;17:35–45.

    CAS  Google Scholar 

  10. Lemanske RF, Guthman JDA, Oertel H, et al. The biological activity of mast cell granules: The effect of vinblastine-induced neutropenia on rat cutaneous late phase reactions. J Immunol 1983;130:2837–2842.

    PubMed  Google Scholar 

  11. Naito Y, Yoshikawa T, Kaneko T, et al. Role of oxygen radicals in indomethacin-induced gastric mucosal microvascular injury in rats. J Clin Gastroenterol 1993;17:S99-S103.

    PubMed  Google Scholar 

  12. Nagamachi Y. Effect of cinchophen on gastric mucosal blood flow and tissue oxygen tension in dogs. In: Umehara S, Ito H (eds) Advances in experimental ulcer. Tokyo: Experimental Ulcer Forum of Japan, 1982;196–204.

    Google Scholar 

  13. Hattori N. Electron microscope studies on acute gastric mucosal lesion of the rat injected with sodium cinchophen solution (in Japanese with English abstract). Kitakanto Igaku (Kitakanto Med J) 1992;42:433–459.

    CAS  Google Scholar 

  14. Nagamachi Y, Hirasawa T, Koida T, Maeda M. Acute gastric mucosal lesions and hemorhcology: Pathogenesis of mucosal edema. Current clinical practice series 33. Tokyo: Excerpta Medica, 1984;172–182.

    Google Scholar 

  15. Grisham MB, Hernandez LA, Granger DN. Xanthine oxidase and neutrophil infiltration in intestinal ischemia. Am J Physiol 1986;251:G567-G574.

    CAS  PubMed  Google Scholar 

  16. Hernandez LA, Grisham MB, Twohig B, et al. Role of neutrophils in ischemia-reperfusion-induced microvascular injury. Am J Physiol 1987;253:H699-H703.

    CAS  PubMed  Google Scholar 

  17. Nagamachi Y. Site of gastric stress ulcerations: Etiological factors. Am J Proctol Gastroenterol. Colon Rectal Surg 1983;34:12–24.

    Google Scholar 

  18. Hirota M, Inoue M, Ando Y, et al. Inhibition of stress-induced gastric mucosal injury by a long-acting superoxide disutase that circulates bound to albumin. Arch Biochem Biophys 1990;280:269–273.

    Article  CAS  PubMed  Google Scholar 

  19. Lewis MS, Whatley RP, Cain P, et al. Hydrogen peroxide stimulates the synthesis of platelet-activating factor by endothelium and induces endothelial cell-dependent neutrophil adhesion. J Clin Invest 1988;82:2045–2055.

    CAS  PubMed  Google Scholar 

  20. Ogle CW, Qiu BS. Nitric oxide inhibition intensifies cold restraint-induced gastric ulcers in rats. Experientia 1993;49:304–307.

    Article  CAS  PubMed  Google Scholar 

  21. Murohara T, Kugiyama K, Sugiyama S, et al. Activated human polymorphonuclear leukocytes elicit endothelium-dependent contraction in isolated pig coronary arteries. J Cardiovasc Pharmacol 1993;21:760–766.

    CAS  PubMed  Google Scholar 

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Takahashi, A., Nagamachi, Y. & Hattori, N. Effects of activated granulocytes and O 2 on microcirculatory injury in acute gastric mucosal lesion in rats induced by sodium cinchophen. J Gastroenterol 31, 153–160 (1996). https://doi.org/10.1007/BF02389511

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  • DOI: https://doi.org/10.1007/BF02389511

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