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Visualization of non-heme ferric and ferrous iron by highly sensitive non-heme iron histochemistry in the stress-induced acute gastric lesions in the rat

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Abstract

Redox-active non-heme iron catalyzes hydroxyl radical \({\text{OH}}^{\raise0.145em\hbox{${\scriptscriptstyle \bullet}$}} \) generation through Haber–Weiss reaction. Oxidative tissue damage by \({\text{OH}}^{\raise0.145em\hbox{${\scriptscriptstyle \bullet}$}} \) has been suggested in the development of stress-induced gastric lesion. Using highly sensitive non-heme iron histochemistry, the perfusion-Perls and -Turnbull methods plus DAB intensification, we studied the distribution of non-heme ferric and ferrous iron (NHF[III] and NHF[II]) in the normal stomach and its changes in the acute gastric lesions induced by restraint water immersion (RWI) stress in the rat. Both NHF[III] and NHF[II] staining increased in the oncotic parietal cells located at the erosive lesion which developed on the gastric mucosal folds after 3 h RWI. It was considered that increase in non-heme iron in these cells catalyzed \({\text{OH}}^{\raise0.145em\hbox{${\scriptscriptstyle \bullet}$}} \) generation under the presence of O ·−2 released from abundant injured mitochondria. This was supported by the increase in H2O2 staining in the erosive region and the obvious reduction of the gastric lesion following administration of deferoxamine before RWI. NHF[II] was stained in the arterial endothelium in the tela submucosa of the normal gastric wall and increase in the entire gastric mucosa after 3 h RWI suggests that the changes in the vascular non-heme iron metabolism were also involved in the response of the stomach to stressful conditions.

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References

  • Agarwal A, Nick HS (2000) Renal response to tissue injury: lessons from heme oxygenase-1 gene ablation and expression. J Am Soc Nephrol 11:965–973

    Google Scholar 

  • Akimoto M (1992) Endothelin levels under water-immersion stress in rats. Nippon Shokakibyo Gakkai Zasshi 89:1982–1989

    Google Scholar 

  • Alencar JL, Chalupsky K, Sarr M, Schini-Kerth V, Vanin AF, Stoclet JC, Muller B (2003) Inhibition of arterial contraction by dinitrosyl-iron complexes: critical role of the thiol ligand in determining rate of nitric oxide (NO) release and formation of releasable NO stores by S-nitrosation. Biochem Pharmacol 66:2365–2374

    Google Scholar 

  • Blake DR, Allen RE, Lunec J (1987) Free radicals in biological systems—a review orientated to inflammatory processes. Br Med Bull 43:371–385

    Google Scholar 

  • Briggs RT, Drath DB, Karnovsky ML, Karnovsky MJ (1975) Localization of NADH oxidase on the surface of human polymorphonuclear leukocytes by a new cytochemical method. J Cell Biol 67:566–586

    Google Scholar 

  • Calatayud S, Barrachina D, Esplugues JV (2001) Nitric oxide: relation to integrity, injury, and healing of the gastric mucosa. Microsc Res Tech 53:325–335

    Google Scholar 

  • Chen YH, Yet SF, Perrella MA (2003) Role of heme oxygenase-1 in the regulation of blood pressure and cardiac function. Exp Biol Med 228:447–453

    Google Scholar 

  • Crichton RR, Ward RJ (1992) Iron metabolism—new perspectives in view. Biochemistry 31:11255–11264

    Google Scholar 

  • Crichton RR, Wilmet S, Legssyer R, Ward RJ (2002) Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells. J Inorg Biochem 91:9–18

    Google Scholar 

  • Das D, Bandyopadhyay D, Bhattacharjee M, Banerjee RK (1997) Hydroxyl radical is the major causative factor in stress-induced gastric ulceration. Free Radic Biol Med 23:8–18

    Google Scholar 

  • Drake IM, Davies MJ, Mapstone NP, Dixon MF, Schorah CJ, White KL, Chalmers DM, Axon AT (1996) Ascorbic acid may protect against human gastric cancer by scavenging mucosal oxygen radicals. Carcinogenesis 17:559–562

    Google Scholar 

  • Gossrau R, Van Noorden CJ, Frederiks WM (1989) Enhanced light microscopic visualization of oxidase activity with the cerium capture method. Histochemistry 92:349–353

    Google Scholar 

  • Gujral JS, Knight TR, Farhood A, Bajt ML, Jaeschke H (2002) Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis? Toxicol Sci 67:322–328

    Google Scholar 

  • Halliwell B, Gutteridge JM (1990) Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 186:1–85

    Google Scholar 

  • Hiraishi H, Terano A, Razandi M, Sugimoto T, Harada T, Ivey KJ (1993) Role of iron and superoxide in mediating hydrogen peroxide injury to cultured rat gastric cells. Gastroenterology 104:780–788

    Google Scholar 

  • Hirokawa M, Miura S, Yoshida H, Kurose I, Shigematsu T, Hokari R, Higuchi H, Watanabe N, Yokoyama Y, Kimura H, Kato S, Ishii H (1998) Oxidative stress and mitochondrial damage precedes gastric mucosal cell death induced by ethanol administration. Alcohol Clin Exp Res 22:111–114

    Google Scholar 

  • Ito M, Shichijo K, Sekine I (1993) Gastric motility and ischemic changes in occurrence of linear ulcer formation induced by restraint-water immersion stress in rat. Gastroenterol Jpn 28:367–373

    Google Scholar 

  • Jacobs DM, Sturtevant RP (1982) Circadian ultrastructural changes in rat gastric parietal cells under altered feeding regiments: a morphometric study. Anat Rec Part A 203:101–113

    Google Scholar 

  • Karam SM (1993) Dynamics of epithelial cells in the corpus of the mouse stomach. IV. Bidirectional migration of parietal cells ending in their gradual degeneration and loss. Anat Rec 236:314–332

    Google Scholar 

  • Kierszenbaum AL (2002) Histology and cell biology. An introduction to pathology. Mosby, St. Louis, MO, pp 409–420

    Google Scholar 

  • Komatsu H (1990) Studies on the mechanism of restraint-induced gastric ulcer—with special reference to mucosal ischemia and gastric secretion. Nippon Shokakibyo Gakkai Zasshi 87:25–38

    Google Scholar 

  • Kwiecien S, Brzozowski T, Konturek SJ (2002) Effects of reactive oxygen species action on gastric mucosa in various models of mucosal injury. J Physiol Pharmacol 53:39–50

    Google Scholar 

  • Levin S, Bucci TJ, Cohen SM, Fix AS, Hardisty JF, LeGrand EK, Maronpot PR, Trump BF (1999) The nomenclature of cell death: recommendations of an ad hoc Committee of the Society of Toxicologic Pathologists. Toxicol Pathol 27:484–490

    Google Scholar 

  • Livingston EH, Howard TJ, Garrick TR, Passaro EP Jr, Guth PH (1991) Strong gastric contractions cause mucosal ischemia. Am J Physiol 260:524–530

    Google Scholar 

  • Loschen G, Azzi A, Richter C, Flohe L (1974) Superoxide radicals as precursors of mitochondrial hydrogen peroxide. FEBS Lett 42:68–72

    Google Scholar 

  • Majno G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146:3–15

    Google Scholar 

  • Manukhina EB, Mashina SYu, Smirin BV, Lyamina NP, Senchikhin VN, Vanin AF, Malyshev IYu (2000) Role of nitric oxide in adaptation to hypoxia and adaptive defense. Physiol Res 49:89–97

    Google Scholar 

  • Meguro R, Asano Y, Iwatsuki H, Shoumura K (2003) Perfusion-Perls and -Turnbull methods supplemented by DAB intensification for nonheme iron histochemistry: demonstration of the superior sensitivity of the methods in the liver, spleen, and stomach of the rat. Histochem Cell Biol 120:73–82

    Google Scholar 

  • Muller B, Kleschyov AL, Alencar JL, Vanin A, Stoclet JC (2002) Nitric oxide transport and storage in the cardiovascular system. Ann NY Acad Sci (2002) 962:131–139

    Google Scholar 

  • Nishida K, Ohta Y, Ishiguro I (1998) Changes in nitric oxide production with lesion development in the gastric mucosa of rats with water immersion restraint stress. Res Commun Mol Pathol Pharmacol 100:201–212

    Google Scholar 

  • Oda M, Han JY, Nakamura M (2000) Endothelial cell dysfunction in microvasculature: relevance to disease processes. Clin Hemorheol Microcirc 23:199–211

    Google Scholar 

  • Parks DA, Williams TK, Beckman JS (1988) Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation. Am J Physiol Gastrointest Liver Physiol 254:768–774

    Google Scholar 

  • Petrat F, De Groot H, Rauen U (2001) Subcellular distribution of chelatable iron: a laser scanning microscopic study in isolated hepatocytes and liver endothelial cells. Biochem J 356:61–69

    Google Scholar 

  • Poss KD, Tonegawa S (1997) Reduced stress defense in heme oxygenase 1-deficient cells. Proc Natl Acad Sci USA 94:10925–10930

    Google Scholar 

  • Price KJ, Hanson PJ, Whittle BJ (1996) Localization of constitutive isoforms of nitric oxide synthase in the gastric glandular mucosa of the rat. Cell Tissue Res 285:157–163

    Google Scholar 

  • Ricevuti G (1997) Host tissue damage by phagocytes. Ann NY Acad Sci 832:426–448

    Google Scholar 

  • Rodriguez J, Maloney RE, Rassaf T, Bryan NS, Feelisch M (2002) Chemical nature of nitric oxide storage forms in rat vascular tissue. Proc Natl Acad Sci USA 100:336–341

    Google Scholar 

  • Said SA, El-Mowafy AM (1998) Role of endogenous endothelin-1 in stress-induced gastric mucosal damage and acid secretion in rats. Regul Pept 73:43–50

    Google Scholar 

  • Sato N, Kawano S, Kamada T, Takeda M (1986) Hemodynamics of the gastric mucosa and gastric ulceration in rats and in patients with gastric ulcer. Dig Dis Sci 31:35–41

    Google Scholar 

  • Sobala GM, Schorah CJ, Sanderson M, Dixon MF, Tompkins DS, Godwin P, Axon AT (1989) Ascorbic acid in the human stomach. Gastroenterology 97:357–363

    Google Scholar 

  • Soesatyo M, Biewenga J, Kraal G, Sminia T (1990) The localization of macrophage subsets and dendritic cells in the gastrointestinal tract of the mouse with special reference to the presence of high endothelial venules. An immuno- and enzyme-histochemical study. Cell Tissue Res 259:587–593

    Google Scholar 

  • Van Noorden CJ, Frederiks WM (1993) Cerium methods for light and electron microscopical histochemistry. J Microsc 171:3–16

    Google Scholar 

  • Vanin AF (1998) Dinitrosyl iron complexes and S-nitrosothiols are two possible forms for stabilization and transport of nitric oxide in biological systems. Biochemistry (Mosc) 63:782–793

    Google Scholar 

  • Yajima N, Hiraishi H, Harada T (1995) Protection of cultured rat gastric cells against oxidant stress by iron chelation. Role of lipid peroxidation. Dig Dis Sci 40:879–886

    Google Scholar 

  • Zhang JF, Zheng F (1997) The role of paraventricular nucleus of hypothalamus in stress-ulcer formation in rats. Brain Res 761:203–209

    Google Scholar 

Download references

Acknowledgements

This work was supported by Grant-in-Aid (14657123) from the Ministry of Education, Culture, Sports and Technology, Japan.

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Correspondence to Yoshiya Asano.

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Asano, Y., Meguro, R., Odagiri, S. et al. Visualization of non-heme ferric and ferrous iron by highly sensitive non-heme iron histochemistry in the stress-induced acute gastric lesions in the rat. Histochem Cell Biol 125, 515–525 (2006). https://doi.org/10.1007/s00418-005-0097-6

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