J Majka

Collegium Medicum of the Jagiellonian University, Cracovia, Lesser Poland Voivodeship, Poland

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Publications (56)189.48 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Hormonal peptides like ghrelin, orexin A (OXA) or nesfatin-1 not only regulate appetite, which is their basic biological function, but also contribute to mechanisms responsible for maintaining integrity of the gastric mucosa. Previous studies including those from our laboratory have revealed that their gastroprotective effect results from cooperation with other factors responsible for protection of the gastric mucosa, including prostaglandin (PG) synthesis pathway, nitric oxide (NO) and the sensory afferent fibres releasing the vasoactive neurotransmitters. The aim of the present study was to determine whether ghrelin, orexin-A (OX-A) or nesfatin-1 with their protective effect on the gastric mucosa, also can modify the healing of chronic gastric ulcers. Furthermore, an attempt was made to explain participation of these peptides in healing processes of chronic gastric ulcers with comorbid conditions for the human beings resulted from diabetes mellitus. In our study, a model of gastric ulcers caused by concentrated acetic acid to induce the chronic gastric ulcers was used, while the clinical condition corresponding to diabetes was induced by single injection of streptozotocin (STZ). We found that ghrelin, OX-A and nesfatin-1 accelerate dynamics of the acetic acid ulcers healing, confirmed by a reduction in the ulcer area and this effect was accompanied by an increase in gastric blood flow at the ulcer margin. Destruction of sensory afferent fibres with capsaicin or blocking of vanilloid receptors with capsazepine resulted in a significant reduction of ghrelin, OX-A and nesfatin-1-induced acceleration of ulcer healing. Similar results were obtained when an NO-synthase blocker, L-NNA was used in a combination with these peptides. Moreover, it was found that OX-A and nesfatin-1 failed to accelerate the healing process under diabetic condition because both these hormones induced reduction in the ulcer area and the increase in blood flow in normal, non-diabetic rats were completely lost in the group of animals with diabetes. Treatment with OX-A and nesfatin-1 increased superoxide dismutase (SOD) mRNA expression even in acetic acid ulcers concurrent with diabetes. However, the treatment with OX-A and nesfatin-1 failed to alter the increase in gastric mucosal mRNA expression for ghrelin and hypoxia-inducible factor 1-alpha (HIF-1α), this latter effect that had been strongly pronounced in diabetic animals. We conclude that the hormonal peptides involved in the regulation of satiety and hunger such as ghrelin, OX-A and nesfatin-1 contribute to the process of chronic gastric ulcers healing cooperating with NO and sensory afferent nerve endings releasing vasoactive neuropeptide CGRP. Furthermore, OX-A and nesfatin-1, the two relatively unrecognized peptides, play an essential role in healing process of chronic gastric ulcers activating the gastric blood flow at ulcer margin and the mucosal regeneration and both ulcer healing and accompanying hyperemia at ulcer margin are greatly impaired during diabetes. Possibly, loss of the healing effect of these peptides during diabetes results from an interaction with radical generation processes as reflected by an increase of mRNA expression for SOD as well as the failure of their attenuating activity on proinflammatory factors such as HIF-1α.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 10/2013; 64(5):625-37. · 2.48 Impact Factor
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    ABSTRACT: Nesfatin-1 belongs to a family of anorexigenic peptides, which are responsible for satiety and are identified in the neurons and endocrine cells within the gut. These peptides have been implicated in the control of food intake, however very little is known concerning its contribution to gastric secretion and gastric mucosal integrity. In this study the effects of nesfatin-1 on gastric secretion and gastric lesions induced in rats by 3.5h of water immersion and restraint stress (WRS) were determined. Exogenous nesfatin-1 (5-40μg/kg i.p.) significantly decreased gastric acid secretion and attenuated gastric lesions induced by WRS, and this was accompanied by a significant rise in plasma NUCB2/nefatin-1 levels, the gastric mucosal blood flow (GBF), luminal NO concentration, generation of PGE2 in the gastric mucosa, an overexpression of mRNA for NUBC2 and cNOS, as well as a suppression of iNOS and proinflammatory cytokine IL-1β and TNF-α mRNAs. Nesfatin-1-induced protection was attenuated by suppression of COX-1 and COX-2 activity, the inhibition of NOS with L-NNA, the deactivation of afferent nerves with neurotoxic doses of capsaicin, and the pretreatment with capsazepine to inhibit vanilloid VR1 receptors. This study shows for the first time that nesfatin-1 exerts a potent protective action in the stomach of rats exposed to WRS and these effects depend upon decrease in gastric secretion, hyperemia mediated by COX-PG and NOS-NO systems, the activation of vagal and sensory nerves and vanilloid receptors.
    Peptides 08/2013; · 2.52 Impact Factor
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    ABSTRACT: Export Date: 20 November 2013, Source: Scopus, doi: 10.5114/pg.2012.33041, Language of Original Document: Polish, Correspondence Address: Brzozowski, T.; Katedra Fizjologii, Uniwersytetu Jagiellońskiego Collegium Medicum, ul. Grzegorzecka 16, 31-531 Kraków, Poland; email: mpbrzozo@cyf-kr.edu.pl, Chemicals/CAS: ghrelin, 304853-26-7; nitric oxide, 10102-43-9; prostaglandin synthase, 39391-18-9, 59763-19-8, 9055-65-6, References: Kanai, Y., Tanuma, S., Purification of a novel B cell growth and differentiation factor associated with lupus syndrome (1992) Immunol Lett, 32, pp. 43-48;
    Przeglad Gastroenterologiczny. 01/2012; 7(6):339-350.
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    11/2011; , ISBN: 978-953-307-976-9
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
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    ABSTRACT: Mixed reflux of the gastroduodenal contents induces the esophageal mucosal damage and inflammation progressing chronic esophagitis and premalignant Barrett's esophagus (BE). The role of cyclooxygenase-2 (COX-2) and chronic inflammation in the progression of BE toward adenocarcinoma of the esophagus has not been extensively studied in experimental models of BE in animals and in human subjects. We evaluated the expression of COX-2 in rat model of BE and examined the usefulness of COX-2 expression in determining the risk of malignant transformation in patients with BE treated with argon plasma coagulation (APC) that allows for effective ablation of metaplastic mucosa (group A) without or with proton pump inhibitors (PPI). In addition, the group B of patients was subjected to laparoscopic Nissen's fundoplication and group K that served as control, received PPI treatment only. Expression of COX-2 was evaluated in fresh-frozen biopsy specimens obtained from the distal esophagus in all 60 patients before and 12 months after treatment. In experimental studies, eighty rats were surgically prepared with esophagogastroduodenal anastomosis (EGDA) resulting in chronic esophagitis. At 4 months, the esophageal damage in EGDA rats was evaluated by macroscopic and histological index score, the plasma IL-1beta and TNF-alpha levels was determined by ELISA and the mucosal expression of COX-2 mRNA and COX-2 protein were assessed by RT-PCR and Western Blot, respectively. Chronic esophagitis was developed in all EGDA animals followed by the rise in the plasma TNF-alpha and IL-1beta levels. Histology revealed extensive esophageal ulcerations with development of columnar epithelium, formation of mucus glands in squamous epithelium, intestinal metaplasia distant to anastomosis consisting of goblet cells, infiltration of inflammatory cells including plasma cells and lymphocytes. COX-2 mRNA was absent in the esophageal mucosa of sham-control animals but strongly upregulated in metaplastic Barrett's epithelium. In BE patients, the overexpression of COX-2 was documented in patients with dysplasia. After APC (group A) or Nissen's fundoplication (group B), the expression of COX-2 mRNA was markedly reduced and these effects were positively correlated with histopathological findings. Controls failed to show significant alterations in COX-2 expression. We conclude that 1) EGDA rats serve as the suitable model of the chronic esophagitis by the gastrointestinal refluxate resembling many features of those observed in human Barrett's esophagus, as confirmed by severe morphology changes, excessive release of proinflammatory cytokines TNF-alpha and IL-1beta and overexpression of COX-2, and 2) the significant correlation of the degree of COX-2 overexpression with histopathological findings indicates the usefulness of this inducible biomarker as a valuable indicator of the risk of malignant transformation in patients with BE.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 08/2010; 61(4):409-18. · 2.48 Impact Factor
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    ABSTRACT: Bile salts play an important pathogenic role in the development of Barrett adenocarcinoma (BA). However, the precise role of different bile salts in this process is still unknown. The aim of the present study was to compare the effects of two different bile salts, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on the expression of COX-2, CDX-2 and DNA repair enzymes (MUTYH, OGG-1) in the Barrett epithelial cancer cells (OE-19). OE-19 cells were incubated with DCAor UDCA(100 microM or 300 microM at pH=7.0) over 24 h. To investigate the involvement of NF kappaB, in separate experiments the cells were incubated with DCA in the presence of proteosome inhibitor (MG-132). Cells cycle and apoptosis were analyzed by FACS analysis. After incubation of OE-19 cells with bile salts, the expression of mRNA of COX-2, DNA repair enzymes (MUTYH, OGG-1) and caudal-related homebox transcription factor CDX-2 were measured by quantitative RT-PCR. OE-19 cell were also transfected with siRNA-RelA (p65) to asses effect of NF kappaB inactivation on COX-2 and CDX2 expression. DCA caused a stronger reduction in cell survival of OE-19 cells than UDCA. In addition, DCA stimulated directly the translocation of NF kappaB p65 (active form) in the nuclei of OE-19 cells. DCA caused stronger than UDCA stimulation of the COX-2 mRNA expression in these cells and this effect was significantly attenuated by the addition of inhibitor of NF kappaB activity (proteosome inhibitor MG-132). siRNA-RelA reduced expression not only of NF kappaB but also expression of COX-2 as well as CDX-2 mRNA. DCA caused stronger downregulation of mRNA for DNA repair enzymes MUTYH and OGG-1 than UDCA. In contrast, UDCA induced stronger CDX-2 mRNA expression than DCA in OE-19 cells. We conclude that bile salts are involved in the carcinogenesis of Barrett adenocarcinoma via inhibition of DNA repair enzymes and induction of COX-2 and this last effect is, at least partly, mediated by NF kappaB. DCA shows carcinogenic potential due to high upregulation of COX-2, CDX-2 and downregulation of DNA repair enzymes.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 04/2010; 61(2):185-92. · 2.48 Impact Factor
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    ABSTRACT: Orexigenic peptides are group of endocrine hormones exerting a pleiotropic influence on many physiological functions including regulation of the feeding behaviour and energy expenditure, release of growth hormone (GH) and inotropic effects on the heart. Some of these peptides such as ghrelin, originally identified in the gastric mucosa, has been involved not only in control of food intake and growth hormone release but also exerts the immunomodulatory and anti-inflammatory properties. This review summarizes the recent attempts to prove the concept that orexigenic peptides such as ghrelin, orexin-A and obestatin besides playing an important role in the mechanism of food intake, exhibit a potent gastroprotective action against the formation of acute gastric mucosal injury induced by various ulcerogens. This protective effect depends upon vagal activity and hyperemia mediated by NOS/NO and COX/PG systems and CGRP released from sensory afferent nerves. In addition, the appetite peptides such as ghrelin and orexin-A are implicated in the mechanism of the healing of preexisting gastric ulcers due to an activation of specific GHS-R1a and OX-R1 receptors and PG/COX system.
    Current pharmaceutical design 02/2010; 16(10):1214-23. · 4.41 Impact Factor
  • Gastroenterology 01/2010; 138(5). · 12.82 Impact Factor
  • Gastroenterology 01/2010; 138(5). · 12.82 Impact Factor
  • Gastroenterology 01/2009; 136(5). · 12.82 Impact Factor
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    ABSTRACT: Infection by Helicobacter pylori (Hp) has been linked to extradigestive pathologies including ischemic cerebral disease. The aim of our study was to assess the relationship between chronic Hp infection and ischemic stroke risk factors. 80 patients (pts) aged 60-75 years with ischemic stroke confirmed by CT scans (group I) and 80 age- and gender-matched healthy controls (group II) were included into trial. Atherosclerotic plaques from 20 Hp positive pts were obtained at carotid endarterectomy for Hp DNA assessment by PCR. In all groups following parameters were determined; 1) the prevalence of Hp infection using (13)C-Urea Breath Test (UBT), 2) plasma anti-Hp and anti-CagA IgG and interleukin-8 (IL-8), and 3) plasma lipids and fibrinogen. Hp positive pts and controls received one-week anti-Hp therapy and after six months total cholesterol, low-density lipoprotein (LDL)-cholesterol, fibrinogen and IL-8 levels were re-examined. Hp infection was detected by UBT in 83.75% of stroke pts but only in 65% of controls. CagA seropositivity was also significantly higher in stroke pts (57.5%) than in controls (33.75%). Plasma levels of cholesterol, LDL-cholesterol and fibrinogen as well as IL-8 were significantly higher in Hp positive subjects, especially in pts with ischemic stroke. Six months following successful anti-Hp therapy, the plasma levels of total cholesterol, LDL-cholesterol, fibrinogen and IL-8 were significantly lower than those in Hp positive stroke pts and controls. Hp infection represents risk factor of ischemic stoke via an interaction of Hp cytotoxins or cytokines with atherosclerotic plaques in carotic arteries.
    Medical science monitor: international medical journal of experimental and clinical research 11/2002; 8(10):CR675-84. · 1.22 Impact Factor
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    ABSTRACT: Helicobacter pylori (Hp) is a common pathogen colonizing the a gastric mucosa, but some reports indicated that it may also be found in the oral cavity, which could serve as a reservoir of the bacteria and a source of gastric reinfection. Accordingly, we aimed to study whether the oral cavity, particularly gingival pockets, are colonized by Hp and whether it could be the source of gastric reinfection. We studied 329 patients with dyspeptic symptoms (257 with chronic gastritis, 15 with gastric ulcer, and 57 with duodenal ulcer). The [13C]urea breath test (UBT), gastroscopy, and Hp culture from gastric biopsies were carried out, and material was collected from the oral cavity (gingival pocket) for bacteriological culture and genomic DNA studies. The serum was obtained for anti-Hp IgG and anti-CagA assays and saliva for anti-Hp IgA determination using the ELISA technique. Bacteria in material from gingival pockets and biopsies from the corpus and antrum of stomach of 30 DU patients before and after Hp eradication were also examined by PCR technique, using primers specific for 16S rRNA. All Hp-positive patients (276) were subjected to one week of triple therapy (omeprazole 2 x 20 mg twice a day, clarithromycin 2 x 500 mg twice a day, and metronidazole 2 x 500 mg twice a day). The measurements described above were then repeated at four weeks and six months. Bacteriological culture showed the presence of Hp in the material from oral cavity in about 50% of patients, whereas UBT, used as a gold standard, revealed gastric Hp infection in about 84% of these patients. The eradication was successful in the majority of patients (87%), but about 13% of them were still Hp positive after four weeks and about 21% after six months. Four weeks after Hp therapy, Hp was found in culture from oral samples in 23% (P < 0.05 vs initial) and after six months in 35.1%. The IgA levels recorded in saliva were in a close agreement with UBT results. Hp DNA assessed by PCR in 30 DUs before eradication of Hp was detected in 95% of antral mucosa, 90% in corpus mucosa, and in 35% of gingival pocket material, and after eradication therapy Hp DNA values fell to 25%, 20%, and 10%, respectively. In conclusion, Hp is commonly detected in the oral cavity of patients with dyspeptic symptoms, but the gastric reinfection does not appear to occur in the patients despite oral Hp colonization.
    Digestive Diseases and Sciences 05/2002; 47(5):978-86. · 2.26 Impact Factor
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    ABSTRACT: Ulcer healing involves expression of various growth factors such as epidermal growth factor (EGF), hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) at the ulcer margin, but the influence of EGF, HGF and bFGF applied locally with or without neutralizing anti-EGF, HGF and bFGF antibodies or cyclooxygenase (COX)-1 and COX-2 inhibitors on ulcer healing and the expression of COX-1 and COX-2 during ulcer healing have only been studied a little. Rats with gastric ulcers induced by serosal application of acetic acid (ulcer area 28 mm2 received a submucosal injection of either (1) vehicle (saline), (2) EGF, (3) HGF, and (4) bFGF with or without antibodies against EGF, HGF and bFGF or indomethacin (2 mg/kg/day i.p.), a nonspecific inhibitor of COX, or NS-398 (10 mg/kg/day i.g.) and Vioxx (5 mg/kg/day i.g.), both highly specific COX-2 inhibitors. A separate group of animals with chronic gastric fistulas was also used to assess gastric secretion during ulcer healing with and without growth factors. Each growth factor and specific antibody against EGF, HGF and bFGF (100 ng/100 microl each) were injected just around the ulcer immediately after ulcer induction and this local injection was repeated on day 2 following anesthesia and laparotomy. On days 13 and 21, the ulcer area was determined by planimetry, gastric blood flow (GBF) at the ulcer margin was examined by the H2-gas clearance technique, and mucosal generation of PGE2 and the gene expression of COX-1 and COX-2 in the non-ulcerated and ulcerated gastric mucosa were assessed. Gastric ulcers healed progressively within 21 days after induction and this effect was accompanied by a significant increase in GBF at the ulcer margin and in the expression of COX-2 in the ulcer area. Local treatment with EGF, HGF and bFGF produced a significant decrease in gastric acid secretion and significantly accelerated the rate of ulcer healing and raised GBF at the ulcer margin causing further significant upregulation of COX-2 but not COX-1 expression in the ulcerated mucosa. The acceleration of ulcer healing and hyperemia at the ulcer margin exhibited by locally applied EGF, HGF and bFGF were similar to those obtained with systemic administration of these growth factors. HGF applied submucosally, upregulated COX-2 expression and this was significantly attenuated by concurrent treatment with antibody against this peptide. Anti-EGF and anti-bFGF antibodies completely abolished the acceleration of the ulcer healing and hyperemia at the ulcer margin induced by these growth factors. Indomethacin and both COX-2 inhibitors significantly prolonged ulcer healing, while suppressing the generation of PGE2 in non-ulcerated and ulcerated gastric mucosa and GBF at the ulcer margin. The acceleration of ulcer healing by EGF, HGF and bFGF and the accompanying rise in GBF at the ulcer margin were significantly attenuated by the concurrent treatment with indomethacin or NS-398 and Vioxx. (1) Growth factors accelerate ulcer healing due to enhancement in the microcirculation around the ulcer and these effects are specific because they can be abolished by neutralization with antibodies; (2) COX-2-derived prostaglandins and suppression of gastric secretion may play an important role in the acceleration of ulcer healing by various growth factors, and (3) the local effects of EGF, HGF and bFGF on ulcer healing can be reproduced by their systemic application indicating the high efficacy of growth factors to accelerate this healing.
    Digestion 02/2001; 64(1):15-29. · 1.94 Impact Factor
  • Gastroenterology 01/2001; 120(5). · 12.82 Impact Factor
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    ABSTRACT: Background/Aims: Ulcer healing involves expression of various growth factors such as epidermal growth factor (EGF), hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) at the ulcer margin, but the influence of EGF, HGF and bFGF applied locally with or without neutralizing anti-EGF, HGF and bFGF antibodies or cyclooxygenase (COX)-1 and COX-2 inhibitors on ulcer healing and the expression of COX-1 and COX-2 during ulcer healing have only been studied a little. Methods: Rats with gastric ulcers induced by serosal application of acetic acid (ulcer area 28 mm2) received a submucosal injection of either (1) vehicle (saline), (2) EGF, (3) HGF, and (4) bFGF with or without antibodies against EGF, HGF and bFGF or indomethacin (2 mg/kg/day i.p.), a nonspecific inhibitor of COX, or NS-398 (10 mg/kg/day i.g.) and Vioxx (5 mg/kg/day i.g.), both highly specific COX-2 inhibitors. A separate group of animals with chronic gastric fistulas was also used to assess gastric secretion during ulcer healing with and without growth factors. Each growth factor and specific antibody against EGF, HGF and bFGF (100 ng/100 μl each) were injected just around the ulcer immediately after ulcer induction and this local injection was repeated on day 2 following anesthesia and laparotomy. On days 13 and 21, the ulcer area was determined by planimetry, gastric blood flow (GBF) at the ulcer margin was examined by the H2-gas clearance technique, and mucosal generation of PGE2 and the gene expression of COX-1 and COX-2 in the non-ulcerated and ulcerated gastric mucosa were assessed. Gastric ulcers healed progressively within 21 days after induction and this effect was accompanied by a significant increase in GBF at the ulcer margin and in the expression of COX-2 in the ulcer area. Local treatment with EGF, HGF and bFGF produced a significant decrease in gastric acid secretion and significantly accelerated the rate of ulcer healing and raised GBF at the ulcer margin causing further significant upregulation of COX-2 but not COX-1 expression in the ulcerated mucosa. The acceleration of ulcer healing and hyperemia at the ulcer margin exhibited by locally applied EGF, HGF and bFGF were similar to those obtained with systemic administration of these growth factors. HGF applied submucosally, upregulated COX-2 expression and this was significantly attenuated by concurrent treatment with antibody against this peptide. Anti-EGF and anti-bFGF antibodies completely abolished the acceleration of the ulcer healing and hyperemia at the ulcer margin induced by these growth factors. Indomethacin and both COX-2 inhibitors significantly prolonged ulcer healing, while suppressing the generation of PGE2 in non-ulcerated and ulcerated gastric mucosa and GBF at the ulcer margin. The acceleration of ulcer healing by EGF, HGF and bFGF and the accompanying rise in GBF at the ulcer margin were significantly attenuated by the concurrent treatment with indomethacin or NS-398 and Vioxx. Conclusions: (1) Growth factors accelerate ulcer healing due to enhancement in the microcirculation around the ulcer and these effects are specific because they can be abolished by neutralization with antibodies; (2) COX-2-derived prostaglandins and suppression of gastric secretion may play an important role in the acceleration of ulcer healing by various growth factors, and (3) the local effects of EGF, HGF and bFGF on ulcer healing can be reproduced by their systemic application indicating the high efficacy of growth factors to accelerate this healing.
    Digestion 01/2001; 64(1):15-29. · 1.94 Impact Factor
  • Gastroenterology 01/2000; 118(4). · 12.82 Impact Factor
  • Gastroenterology 01/2000; 118(4). · 12.82 Impact Factor
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    ABSTRACT: Melatonin, a pineal hormone, is known to scavenge oxygen free radicals and to be present in the gut but little is known about its role in the protection of gastric mucosa against the damage accompanied by a marked increase in these radicals. This study was designed to determine the effects of melatonin on the formation of acute gastric lesions induced by ischemia-reperfusion and, for comparison, by a topical irritant such as 100% ethanol. It was found that pretreatment with melatonin at a dose of 5 mg/kg given intragastrically reduced significantly gastric lesions induced by ischemia-reperfusion and this was accompanied by a reduction in free radicals in the blood and by attenuation of the fall in gastric blood flow. In contrast, melatonin failed to affect acute gastric lesions induced by 100% ethanol. We conclude that melatonin is capable of protecting gastric mucosa from the damage caused by ischemia-reperfusion and that this action is mediated, at least in part, by limitation of the generation of free radicals and by attenuation of the fall in gastric blood flow.
    European Journal of Pharmacology 04/1997; 322(1):73-7. · 2.59 Impact Factor
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    ABSTRACT: Ammonia (NH4OH) generated by urease from urea in the Helicobacter pylori (Hp)-infected stomach is considered as a one of the major pathogenic factors in the Hp-associated gastritis but the mechanism of the deleterious action of NH4OH on gastric mucosa has not been fully explained. In this study, the gastric mucosa was exposed to topical NH4OH in various concentrations (15-250 mM) (series A) and to NH4OH in a small concentration followed by a high concentration (250 mM) of NH4OH (series B) or to the combination of urea and urease to generate NH4OH (series C) followed by 250 mM NH4OH in order to determine the "mild irritant" and protective properties of this substance on the mucosa. Administration of NH4OH alone resulted in a concentration-dependent mucosal damage starting at 30 mM and reaching at 250 mM the degree similar to that obtained with 100% ethanol. The acute mucosal damage by NH4OH was accompanied by the fall in gastric blood flow reaching nadir at 250 mM NH4OH of about 30% of the normal value. When the mucosa was first exposed to low concentration of NH4OH (15 mM) and then insulted with its larger concentration (250 mM), the lesion area was markedly reduced as compared to that obtained with 250 mM NH4OH alone and this effect was accompanied by a significant rise in the GBF. This adaptive cytoprotection by 15 mM NH4OH was reversed, in part, by the pretreatment with indomethacin to inhibit prostaglandins (PG) or L-NAME to suppress nitric oxide (NO) formation or after capsaicin-induced denervation of sensory nerves. Blockade of endogenous sulfhydryls (SH) by N-ethylmaleimide (NEM) eliminated this adaptive cytoprotection but the suppression of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, by alpha-difluoro methylornithine (DFMO) failed to influence the protection and accompanying hyperemia afforded by NH4OH in low concentration. The combination of urea (2%) and urease (100 U), which raised the gastric luminal NH4OH concentration by about 5-folds, also reduced significantly the lesions provoked by 250 mM NH4OH. This protection and accompanying hyperemia induced was significantly attenuated by the pretreatment with indomethacin or hydroxyurea, a potent urease inhibitor. Hydroxyurea abolished completely the rise in luminal NH4OH produced by the combined treatment of urea plus urease. We conclude that 1) NH4OH in high concentration damages the gastric mucosa but when applied at lower concentration or generated in the stomach by urea-urease system, acts as local mild irritant to induce adaptive cytoprotection that probably involves PG, sensory nerves and arginine-NO-pathaway.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 04/1996; 47(1):137-50. · 2.48 Impact Factor

Publication Stats

660 Citations
189.48 Total Impact Points

Institutions

  • 2012
    • Collegium Medicum of the Jagiellonian University
      Cracovia, Lesser Poland Voivodeship, Poland
  • 1994–2011
    • Jagiellonian University
      • • Department of Physiology
      • • Medical College
      Kraków, Lesser Poland Voivodeship, Poland
  • 1994–1995
    • Rutgers New Jersey Medical School
      • New Jersey Dental School
      Newark, NJ, United States
  • 1993
    • Krakow University Hospital
      Cracovia, Lesser Poland Voivodeship, Poland