Molecular and Cellular Biochemistry

, Volume 253, Issue 1–2, pp 329–338

Smoking and the pathogenesis of gastroduodenal ulcer – recent mechanistic update

  • Pallab Maity
  • Kaushik Biswas
  • Somenath Roy
  • Ranajit K. Banerjee
  • Uday Bandyopadhyay


Peptic ulcer is a common disorder of gastrointestinal system and its pathogenesis is multifactorial, where smoking and nicotine have significant adverse effects. Smoking and chronic nicotine treatment stimulate basal acid output which is more pronounced in the smokers having duodenal ulcer. This increased gastric acid secretion is mediated through the stimulation of H2-receptor by histamine released after mast cell degranulation and due to the increase of the functional parietal cell volume or secretory capacity in smokers. Smoking and nicotine stimulate pepsinogen secretion also by increasing chief cell number or with an enhancement of their secretory capacity. Long-term nicotine treatment in rats also significantly decreases total mucus neck cell population and neck-cell mucus volume. Smoking also increases bile salt reflux rate and gastric bile salt concentration thereby increasing duodenogastric reflux that raises the risk of gastric ulcer in smokers. Smoking and nicotine not only induce ulceration, but they also potentiate ulceration caused by H. pylori, alcohol, nonsteroidal anti-inflammatory drugs or cold restrain stress. Polymorphonuclear neutrophils (PMN) play an important role in ulcerogenesis through oxidative damage of the mucosa by increasing the generation of reactive oxygen intermediates (ROI), which is potentiated by nicotine and smoking. Nicotine by a cAMP-protein kinase A signaling system elevates the endogenous vasopressin level, which plays an aggressive role in the development of gastroduodenal lesions. Smoking increases production of platelet activating factor (PAF) and endothelin, which are potent gastric ulcerogens. Cigarette smoking and nicotine reduce the level of circulating epidermal growth factor (EGF) and decrease the secretion of EGF from the salivary gland, which are necessary for gastric mucosal cell renewal. Nicotine also decreases prostaglandin generation in the gastric mucosa of smokers, thereby making the mucosa susceptible to ulceration. ROI generation and ROI-mediated gastric mucosal cell apoptosis are also considered to be important mechanism for aggravation of ulcer by cigarette smoke or nicotine. Both smoking and nicotine reduce angiogenesis in the gastric mucosa through inhibition of nitric oxide synthesis thereby arresting cell renewal process. Smoking or smoke extract impairs both spontaneous and drug-induced healing of ulcer. Smoke extract also inhibits gastric mucosal cell proliferation by reducing ornithine decarboxylase activity, which synthesises growth-promoting polyamines. It is concluded that gastric mucosal integrity is maintained by an interplay of some aggressive and defensive factors controlling apoptotic cell death and cell proliferation and smoking potentiates ulcer by disturbing this balance.

smoking nicotine gastro-duodenal ulcer reactive oxygen intermediates neutrophil mucosal apoptosis gastric aggressive factors gastroprotective factors 


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  1. 1.
    Miller TA: Mechanism of stress-related mucosal damage. Am J Med 83: 8-14, 1987Google Scholar
  2. 2.
    Das D, Banerjee RK: Effect of stress on the antioxidant enzymes and gastric ulceration. Mol Cell Biochem 125: 115-125, 1993Google Scholar
  3. 3.
    Das D, Bandyopadhyay D, Bhattacharjee M, Banerjee RK: Hydroxyl radical is the major causative factor in stress-induced gastric ulceration. Free Radic Biol Med 23: 8-18, 1997Google Scholar
  4. 4.
    Langman MJS, Brooks P, Hawkey CJ, Silverstein F, Yeomans N: Nonsteroidal anti-inflammatory drug associated ulcer: Epidemiology, causation and treatment. J Gastroenterol Hepatol 6: 442-449, 1991Google Scholar
  5. 5.
    Ivey KJ: Mechanisms of nonsteroidal anti-inflammatory drug-induced gastric damage. Action of therapeutic agents. Am J Med 84(suppl 2A): 41-48, 1988Google Scholar
  6. 6.
    Goodwin CS, Armstrong JA, Marshall BJ: Campylobacter pylories, gastritis and peptic ulceration. J Clin Pathol 39: 353-365, 1986Google Scholar
  7. 7.
    Konturek PC, Konturek SJ: Role of Helicobacter pylori infection in gastro-duodenal secretion and in pathogenesis of peptic ulcer and gastritis. J Physiol Pharmacol 45: 333-350, 1994Google Scholar
  8. 8.
    Bhattacharjee M, Bhattacharjee S, Gupta A, Banerjee RK: Critical role of an endogenous gastric peroxidase in controlling oxidative damage in H. pylori-mediated and non-mediated gastric ulcer. Free Radic Biol Med 32: 731-743, 2002Google Scholar
  9. 9.
    Wallace JL, Granger DN: The cellular and molecular basis of gastric mucosal defense. FASEB J 10: 731-740, 1996Google Scholar
  10. 10.
    Phull PS, Green CJ, Jacyna MR: A radical view of stomach: The role of oxygen-derived free radicals and antioxidants in gastroduodenal disease. Eur J Gastroenterol Hepatol 7: 265-274, 1995Google Scholar
  11. 11.
    Guslandi M: A radical view of Helicobactor pylori. Am J Gastroenterol 94: 2797-2798, 1999Google Scholar
  12. 12.
    Konturek PC, Brzozowski T, Konturek SJ, Pajdo R, Konturek JE, Kwiecien S, Taut A, Hahn EG: Apoptosis in gastric mucosa with stress-induced gastric ulcers. J Physiol Pharmacol 50: 211-225, 1999Google Scholar
  13. 13.
    Piotrowski J, Piotrowski E, Skrodzka D, Slomiani A, Slomiany BL: Gastric mucosal apoptosis induced by ethanol: Effect of antiulcer agents. Biochem Mol Biol Int 42: 247-254, 1997Google Scholar
  14. 14.
    Slomiany BL, Piotrowski E, Slomiany A: Induction of tumor necrosis factor-α and apoptosis in the gastric mucosal injury by indomethacin: Effect of omeprazole and ebrotidine. Scand J Gastroenterol 32: 638-642, 1997Google Scholar
  15. 15.
    Kohda K, Tanaka K, Aiba Y, Yasuda M, Miwa T, Koga Y: Role of apoptosis induced by Helicobacter pylori infection in the development of duodenal ulcer. Gut 44: 456-462, 1999Google Scholar
  16. 16.
    Watanabe S, Takagi A, Koga Y, Kamiya S, Miwa T: Helicobacter pylori induces apoptosis in gastric epithelial cells through inducible nitric oxide. J Gastroenterol Hepatol 15: 168-174, 2000Google Scholar
  17. 17.
    Szabo I, Tarnawski AS: Apoptosis in the gastric mucosa: Molecular mechanisms, basic and clinical implications. J Physiol Pharmacol 51: 3-15, 2000Google Scholar
  18. 18.
    Preziosi R, Sarli G, Marcato PS: Cell proliferation and apoptosis in the pathogenesis of oesophagogastric lesions in pigs. Res Vet Sci 68: 189-196, 2000Google Scholar
  19. 19.
    Peto R: Smoking and death: The past 40 years and the next 40. BMJ 309: 937-939, 1994Google Scholar
  20. 20.
    Eastwood GL: Is smoking still important in the pathogenesis of peptic ulcer disease? J Clin Gastroenterol 25: S1-S7, 1997Google Scholar
  21. 21.
    Endoh K, Leung FW: Effects of smoking and nicotine on the gastric mucosa: A review of clinical and experimental evidence. Gastroenterology 107: 864-878, 1994Google Scholar
  22. 22.
    Ainley CC, Forgacs IC, Keeling PW, Thompson RP: Outpatient endoscopic survey of smoking and peptic ulcer. Gut 27: 648-651, 1986Google Scholar
  23. 23.
    Wong D, Ogle CW: Chronic parenterally administered nicotine and stress-or ethanol-induced gastric mucosal damage in rats. Eur J Pharmacol 292: 157-162, 1995Google Scholar
  24. 24.
    Chow JY, Ma L, Cho CH: An experimental model for studying passive cigarette smoking effects on gastric ulceration. Life Sci 58: 2415-2422, 1996Google Scholar
  25. 25.
    Kurata JH, Elashoff JD, Nogawa AN, Haile BM: Sex and smoking differences in duodenal ulcer mortality. Am J Public Health 76: 700-702, 1986Google Scholar
  26. 26.
    Brenna E, Zahlsen K, Marvik R, Nilsen T, Nilsen OG, Waldum HL: Effects of nicotine on the enterochromaffin like cells of the oxyntic mucosa of the rats. Life Sci 53: 21-29, 1993Google Scholar
  27. 27.
    Salim AS: Allopurinol and dimethyl sulfoxide improve treatment outcomes in smokers with peptic ulcer disease. J Lab Clin Med 119: 702-709, 1992Google Scholar
  28. 28.
    Wang H, Ma L, Li Y, Cho H: Exposure of cigarette smoke increases apoptosis in the rat gastric mucosa through a reactive oxygen species-mediated and p53-independent pathway. Free Radic Biol Med 28: 1125-1131, 2000Google Scholar
  29. 29.
    Parente F, Lazzaroni M, Sangaletti O, Baroni S, Bianchi Porro G: Cigarette smoking, gastric acid secretion, and serum pepsinogen I concentrations in duodenal ulcer patients. Gut 26: 1327-1332, 1985Google Scholar
  30. 30.
    Mertz DP, Thongbhoubesra T: Effect of nicotine on the production of gastric acid (author's transl) Med Klin 71: 150-155, 1976Google Scholar
  31. 31.
    Ligny G, Van Ccauter J, Henry JP: The effect of cigarette smoking on the cicatrization of duodenal ulcers in patients with cimetidine. The role of acid hypersecretion. Rev Med Brux 10: 233-238, 1989Google Scholar
  32. 32.
    Walker V, Taylor WH: Cigarette smoking, chronic peptic ulceration, and pepsin 1 secretion. Gut 20: 971-976, 1979Google Scholar
  33. 33.
    Chang FY, Cheng JT, Lee FY, Wang TF, Lai KH, Lee SD, Tsai YT: Serum pepsinogen I levels in patients with non-ulcer dyspepsia. J Gastroenterol Hepatol 5: 271-276, 1990Google Scholar
  34. 34.
    Pavo I, Morschl E, Szepes Z, Kiss J, Boda K, Vetro G, Varga C, Laszlo FA, Laszlo F: Vasopressin deficiency decreases the frequency of gastroduodenal ulceration in humans. J Physiol Paris 94: 63-66, 2000Google Scholar
  35. 35.
    Laszlo F, Pavo I, Szepes Z, Varga CS, Laszlo FA: Deleterious action of vasopressin in gastroduodenal ulceration: Experimental and clinical observations. Scand J Gastroenterol 228: 62-67, 1998Google Scholar
  36. 36.
    Hollt V, Horn G: Effects of nicotine on mRNA levels encoding opioid peptides, vasopressin and α3 nicotinic receptor subunit in the rat. Clin Invest 70: 224-231, 1992Google Scholar
  37. 37.
    Shioda S, Yada T, Muroya S, Takigawa M, Nakai Y: Nicotine increases Ca2+ in vasopressin neurons. Neurosci Res 29: 311-318, 1997Google Scholar
  38. 38.
    Muller-Lissner SA: Bile reflux is increased in cigarette smokers. Gastroenterology 90: 1205-1209, 1986Google Scholar
  39. 39.
    Rosam AC, Wallace JL, Whittle BJ: Potent ulcerogenic actions of platelet-activating factor on the stomach. Nature 319: 54-56, 1986Google Scholar
  40. 40.
    Etienne A, Thonier F, Hecquet F, Braquet P: Role of neutrophils in gastric damage induced by platelet activating factor. Naunyn Schmiedebergs Arch Pharmacol 338: 422-425, 1988Google Scholar
  41. 41.
    Wallace JL, Cirino G, De Nucci G, McKnight W, MacNaughton WK: Endothelin has potent ulcerogenic and vasoconstrictor actions in the stomach. Am J Physiol Gastrointest Liver Physiol 256: G661-G666, 1989Google Scholar
  42. 42.
    Spyridon L, Akira N, Hiromasa K, Katsutoshi G, Takao M, Yoshiki O, Hideo S, Hisayuki F: The development of the endothelin-1-induced gastric ulcer: time sequence analysis of morphologic changes. Int J Exp Pathol 75: 345-555, 1994Google Scholar
  43. 43.
    Tanus-Santos JE, Sampaio RC, Hyslop S, Franchini KG, Moreno H Jr: Endothelin ET(A) receptor antagonism attenuates the pressor effects of nicotine in rats. Eur J Pharmacol 396: 33-37, 2000Google Scholar
  44. 44.
    Hung CR: Role of histamine in aggravation of gastric acid back-diffusion and vascular permeability in septic rats. Chin J Physiol 44: 199-206, 2001Google Scholar
  45. 45.
    Chow JY, Ma L, Cho CH: Involvement of free radicals and histamine in the potentiating action of cigarette smoke exposure on ethanol-induced gastric mucosal damage in rats. Free Radic Biol Med 24: 1285-1293, 1998Google Scholar
  46. 46.
    Ogle CW, Qiu BS, Cho CH: Nicotine and gastric ulcers in stress. J Physiol Paris 87: 359-365, 1993Google Scholar
  47. 47.
    Ko JK, Cho CH: Alcohol drinking and cigarette smoking: A 'partner' for gastric ulceration. Zhonghua Yi Xue Za Zhi (Taipei) 63: 845-854, 2000Google Scholar
  48. 48.
    Chow JY, Ma L, Zhu M, Cho CH: The potentiating actions of cigarette smoking on ethanol-induced gastric mucosal damage in rats. Gastroenterology 113: 1188-1197, 1997Google Scholar
  49. 49.
    Wong SH, Ogle CW, Cho CH: The influence of chronic or acute nicotine pretreatment on ethanol-induced gastric ulceration in the rats. J Pharma Pharmacol 38: 537-540, 1986Google Scholar
  50. 50.
    Qiu BS, Cho CH, Ogle CW: The influence of chronic nicotine treatment on stress-induced gastric ulceration and emptying rate in rats. Experientia 48: 389-391, 1992Google Scholar
  51. 51.
    Wong D, Koo MW, Shin VY, Liu ES, Cho CH: Pathogenesis of nicotine treatment and its withdrawal on stress-induced gastric ulceration in rats. Eur J Pharmacol 434: 81-86, 2002Google Scholar
  52. 52.
    Tariq M, Parmar NS, Ageel AM: Effect of nicotine and alcohol pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine in rats. Alcohol Clin Exp Res 10: 213-216, 1986Google Scholar
  53. 53.
    Bruggeman TM, Wood JG, Devenport HW: Local control of blood flow in the dog's stomach: vasodilatation caused by acid back-diffusion following topical application of salicylic acid. Gastroenterology 77: 736-744, 1979Google Scholar
  54. 54.
    Ma L, Chow JY, Cho CH: Mechanistic study of adverse actions of cigarette smoke exposure on acetic acid-induced gastric ulceration in rats. Life Sci 62: 257-266, 1998Google Scholar
  55. 55.
    Ma JJ, Hou DQ, Zhang QB, Korsten MA: Reversal of the gastric effects of nicotine by nitric oxide donor treatment. Digestion 63: 102-107, 2001Google Scholar
  56. 56.
    Chujoh C, Nakazawa S: Experimental study for the gastric mucosal damage-especially, the effect of cigarette smoking on the healing course of acetic acid ulcer in rats. Jpn J Gastroenterol 78: 2285-2294, 1981Google Scholar
  57. 57.
    Fletcher DR, Shulkes A, Hardy KJ: The effect of cigarette smoking on gastric acid secretion and gastric mucosal blood flow in man. Aust NZ J Med 15: 417-420, 1985Google Scholar
  58. 58.
    Battistel M, Plebani M, Mario F Di, Lippe LT, Holzer P: Chronic nicotine intake causes vascular dysregulation in the rat gastric mucosa. Gut 34: 1688-1692, 1993Google Scholar
  59. 59.
    Dai S, Ogle CW, Cho CH: Effects of carbenoxolone sodium on gastric and duodenal mucus synthesis in mice. Pharmacology 33: 58-60, 1986Google Scholar
  60. 60.
    Ma L, Wang WP, Chow JY, Lam SK, Cho CH: The role of polyamines in gastric mucus synthesis inhibited by cigarette smoke or its extract. Gut 47: 170-177, 2000Google Scholar
  61. 61.
    Ma L, Liu ES, Chow JY, Wang JY, Cho CH: Interactions of EGF and ornithine decarboxylase activity in the regulation of gastric mucus synthesis in cigarette smoke exposed rats. Chin J Physiol 42: 137-143, 1999Google Scholar
  62. 62.
    Jarvis LR, Whitehead R: Effects of nicotine on the morphology of the rat gastric mucosa. Gastroenterology 78: 1488-1494, 1980Google Scholar
  63. 63.
    Sarosiek J, Jensen RT, Maton PN, Peura DA, Harlow D, Feng T, McCallum RW, Pisegna JR: Salivary and gastric epidermal growth factor in patients with Zollinger-Ellison syndrome: Its protective potential. Am J Gastroenterol 95: 1158-1165, 2000Google Scholar
  64. 64.
    Perez Aisa A, Sopena Biarge F, Arceiz Gonzalo E, Sainz Samitier R, Ortego Diez De Retana J, Lanas Arbeloa A: Effect of exogenous administration of platelet-derived growth factor and epidermal growth factor on duodenal ulcer healing in rats treated with indomethacin. Gastroenterol Hepatol 25: 299-305, 2002Google Scholar
  65. 65.
    Jeffrey SC, Murray MJ, Eichorn ES: Distribution of epidermal growth factor receptor (EGFr) in normal and acute peptic-injured equine gastric squamous epithelium. Equine Vet J 33: 562-569, 2001Google Scholar
  66. 66.
    Pai R, Tarnawski A: Signal transduction cascades triggered by EGF receptor activation: relevance to gastric injury repair and ulcer healing. Dig Dis Sci 43: 14S-22S, 1998Google Scholar
  67. 67.
    Hase S, Nakazawa S, Tsukamoto Y, Segawa K: Effects of prednisolone and human epidermal growth factor on angiogenesis in granulation tissue of gastric ulcer induced by acetic acid. Digestion 42: 135-142, 1989Google Scholar
  68. 68.
    Ma L, Wang WP, Chow JY, Yuen ST, Cho CH. Reduction of EGF is associated with the delay of ulcer healing by cigarette smoking. Am J Physiol Gastrointest Liver Physiol 278: G10-G17, 2000Google Scholar
  69. 69.
    Jones PD, Hudson N, Hawkey CJ: Depression of salivary epidermal growth factor by smoking. BMJ 304: 480-481, 1992Google Scholar
  70. 70.
    Murthy SN, Dinoso VP Jr, Natrajan R: Neurohormonal mechanisms of cigarette smoke-induced duodenal mucosal bicarbonate secretion in the rat. Peptides 18: 1061-1066, 1997Google Scholar
  71. 71.
    Murthy SN, Dinoso VP Jr, Clearfield HR, Chey WY: Simultaneous measurement of basal pancreatic, gastric acid secretion, plasma gastrin, and secretin during smoking. Gastroenterology 73: 758-761, 1977Google Scholar
  72. 72.
    Miller TA: Protective effects of prostaglandins against gastric mucosal damage: Current knowledge and proposed mechanisms. Am J Physiol 254: G601-G623, 1983Google Scholar
  73. 73.
    Quimby GF, Bonnice CA, Burstein SH, Eastwood GL: Active smoking depresses prostaglandin synthesis in human gastric mucosa. Ann Intern Med 104: 616-619, 1986Google Scholar
  74. 74.
    Lam SK: Prostaglandins for duodenal ulcer. Clin Invest Med 10: 232-237, 1987Google Scholar
  75. 75.
    Lindell G, Bukhave K, Lilja I, Madsen JR, Graffner H: Acute effects of high-dose intragastric nicotine on mucosal defense mechanisms: An analysis of nicotine, prostaglandin E2, phospholipase A2, and phospholipids. Dig Dis Sci 42: 640-644, 1997Google Scholar
  76. 76.
    Wenner J, Gunnarsson T, Graffber H, Lindell G: Influence of smoking and Helicobacter pylori on gastric phospholipids. Dig Dis Sci 45: 1648-1352, 2000Google Scholar
  77. 77.
    Cho CH: Current roles of nitric oxide in gastrointestinal disorders. J Physiol Paris 95: 253-256, 2001Google Scholar
  78. 78.
    Jones MK, Tomikawa M, Mohajer B, Tarnawski AS: Gastrointestinal mucosal regeneration: Role of growth factors. Front Biosci 4: D303-D309, 1999Google Scholar
  79. 79.
    Das D, Bandyopadhyay D, Banerjee RK: Oxidative inactivation of gastric peroxidase by site-specific generation of hydroxyl radical and its role in stress-induced gastric ulceration. Free Radic Biol Med 24: 460-469, 1998Google Scholar
  80. 80.
    Bridges RB, Fu MC, Rehm SR: Increased myeloperoxidase activity associated with cigarette smoking. Eur J Resp Dis 67: 84-93, 1985Google Scholar
  81. 81.
    Bosken CH, Doerschuk CM, English D, Hogg JC: Neutrophil kinetics during active cigarette smoking in rabbits. J Appl Physiol 71: 630-637, 1991Google Scholar
  82. 82.
    Gillespie MN, Owasoyo, Kojima S, Jay M: Enhanced chemotaxis and superoxide anion production by polymorphonuclear leukocytes from nicotine-treated and smoke-exposed rats. Toxicology 45: 45-52, 1987Google Scholar
  83. 83.
    Aoshiba K, Nagai A, Yasui S, Konno K: Nicotine prolongs neutrophil survival by suppressing apoptosis. J Lab Clin Med 127: 186-194, 1996Google Scholar
  84. 84.
    Murphy EA, Danna-Leopes D, Sarfati I, Rao SK, Cohen JR: Nicotinestimulated elastase activity release by neutrophils in patients with abdominal aortic aneurysms. Ann Vasc Surg 12: 41-45, 1998Google Scholar
  85. 85.
    Lebargy F, Benhammou K, Morin D, Zini R, Urien S, Bree F, Bignon J, Branellec A, Lagrue G: Tobacco smoking induces expression of very-high-affinity nicotine binding sites on blood polymorphonuclear cells. Am J Respir Crit Care Med 153: 1056-1063, 1996Google Scholar
  86. 86.
    Benhammou K, Lee M, Strook M, Sullivan B, Logel J, Raschen K, Gotti C, Leonard S: [(3)H]Nicotine binding in peripheral blood cells of smokers is correlated with the number of cigarettes smoked per day. Neuropharmacology 39: 2818-2829, 2000Google Scholar
  87. 87.
    Keates S, Hitti YS, Upton M, Kelly CP: Helicobactor pylori infection activates NF-κB in gastric epithelial cells. Gastroenterology 113: 1099-1109, 1997Google Scholar
  88. 88.
    Shimoyama T, Fukuda S, Liu Q, Nakaji S, Munakata A, Sugawara K: Ecabet sodium inhibits the ability of Helicobactor pylori to induce neutrophil production of reactive oxygen species and interleukin-8. J Gastroenterol 36: 153-157, 2001Google Scholar
  89. 89.
    Mooney C, Keenan J, Munster D, Wilson I, Allardyce R, Bagshow P, Chapman B, Chadwick V: Neutrophil activation by Helicobactor pylori. Gut 32: 853-857, 1991Google Scholar
  90. 90.
    Ma L, Chow JY, Cho CH: Cigarette smoking delays ulcer healing: Role of constitutive nitric oxide synthase in rat stomachs. Am J Physiol Gastrointest Liver Physiol 276: G238-G248, 1999Google Scholar
  91. 91.
    Wallace JL, Ma L: Inflammatory mediators in gastrointestinal defense and injury. Exp Biol Med 226: 1003-1015, 2001Google Scholar
  92. 92.
    Jones MK, Wang H, Peskar BM, Levin E, Hani RM, Sarfeh IJ, Tarnawski AS: Inhibition of angiogenesis by nonsteroidal antiinflammatory drugs: Insight into mechanisms and implications for cancer growth and ulcer healing. Nature Med 5: 1418-1423, 1999Google Scholar
  93. 93.
    Ma L, Chow JY, Cho CH: Effects of cigarette smoking on gastric ulcer formation and healing: Possible mechanisms of action. J Clin Gastroenterol 27: S80-S86, 1998Google Scholar
  94. 94.
    Fuji Y, Matsura T, Kai M, Matsui H, Kawasaki H, Yamada K: Mitochondrial cytochrome c release and caspase-3-like protease activation during indomethacin-induced apoptosis in rat gastric mucosal cells. Proc Soc Exp Biol Med 224: 102-108, 2000Google Scholar
  95. 95.
    Wang HY, Ma L, Li Y, Cho CH: The role of nitric oxide on cigarette smoke-induced programmed cell death in the gastric mucosa. Scand J Gastroenterol 36: 235-240, 2001Google Scholar
  96. 96.
    Ma L, Wang HY, Chow JY, Cho CH: Cigarette smoke increases apoptosis in the gastric mucosa: Role of epidermal growth factor. Digestion 60: 461-468, 1999Google Scholar
  97. 97.
    Thornberry NA, Lazebnik Y: Caspases: Enemies within. Science 281: 1312-1316, 1998Google Scholar
  98. 98.
    Shimatsu K, Wanless IR: Role of ischemia in causing apoptosis, atrophy, and nodular hyperplasia in human liver. Hepatology 145: 1323-1336, 1997Google Scholar
  99. 99.
    Gillardon F, Lenz C, Waschke KF, Krajewski S, Reed JC, Zimmermann M, Kuschinsky W: Altered expression of Bcl-2, Bcl-X, Bax, and c-Fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats. Brain Res Mol Brain Res 40: 254-260, 1996Google Scholar
  100. 100.
    Kim JM, Kim JS, Jung HC, Song IS, Kim CY: Apoptosis of human gastric epithelial cells via caspase-3 activation in response to Helicobacter pylori infection: Possible involvement of neutrophils through tumor necrosis factor alpha and soluble Fas ligands. Scand J Gastroenterol 35: 40-48, 2000Google Scholar
  101. 101.
    Konturek SJ, Dembinski A, Warzecha Z, Brzozowski T, Gregory H: Role of epidermal growth factor in healing of chronic gastroduodenal ulcers in rats. Gastroenterology 94: 1300-1307, 1988Google Scholar
  102. 102.
    Konturek SJ, Brzozowski T, Majka J, Pytko-Polonczyk J, Stachura J: Inhibition of nitric oxide synthase delays healing of chronic gastric ulcers. Eur J Pharmacol 239: 215-217, 1993Google Scholar
  103. 103.
    Hetzel DJ, Korman MG, Hansky J, Shearman DJ, Eaves ER, Schmidt GT, Hecker R, Fitch RJ: The influence of smoking on the healing of duodenal ulcer treated with oxmetidine or cimetidine. Aust NZ J Med 13: 587-590, 1983Google Scholar
  104. 104.
    Holstege A: Effects of nicotine, alcohol and caffeine on the incidence, healing and recurrence rate of peptic ulcer. Z Gastroenterol 3: 33-40, 1987Google Scholar
  105. 105.
    Shin VY, Liu ES, Koo MW, Wang JY, Matsui H, Cho CH: Cigarette smoke extracts delay wound healing in the stomach: Involvement of polyamine synthesis. Exp Biol Med (Maywood) 227: 114-124, 2002Google Scholar
  106. 106.
    Gugler R, Rohner HG, Kratochvil P, Brandstatter G, Schmitz H: Effect of smoking on duodenal ulcer healing with cimetidine and oxmetidine. Gut 23: 866-871, 1982Google Scholar
  107. 107.
    Korman MG, Hansky J, Merrett AC, Schmidt GT: Ranitidine in duodenal ulcer: Incidence of healing and effect of smoking. Dig Dis Sci 27: 712-715, 1982Google Scholar
  108. 108.
    Freston JW: Mechanisms of relapse in peptic ulcer disease. J Clin Gastroenterol 11: S34-S38, 1989Google Scholar
  109. 109.
    Lam SK, Hui WM, Lau WY, Branicki FJ, Lai CL, Lok AS, Ng MM, Fok PJ, Poon GP, Choi TK: Sucralfate overcomes adverse effect of cigarette smoking on duodenal ulcer healing and prolongs subsequent remission. Gastroenterology 92: 1193-201, 1987Google Scholar
  110. 110.
    Glise H, Carling L, Hallerbaeck B, Halgren T, Kagevi I, Solhaug JH, Svedberg LE, Waehlby L: Relapse rate of healed duodenal, pyloric, and gastric ulcers treated either with sucralfate or cimetidine. Am J Med 83: 105-109, 1987Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Pallab Maity
    • 1
  • Kaushik Biswas
    • 2
  • Somenath Roy
    • 1
  • Ranajit K. Banerjee
    • 2
  • Uday Bandyopadhyay
    • 2
  1. 1.Immunology and Microbiology Laboratory, Department of Human Physiology with Community HealthVidyasagar UniversityMidnaporeIndia
  2. 2.Department of PhysiologyIndian Institute of Chemical BiologyKolkataIndia

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