AGE-RELATED CHANGES IN PROSTAGLANDIN E2, NITRIC OXIDE, AND VASCULAR ENDOTHELIAL GROWTH FACTOR LEVELS IN GASTRIC MUCOSA DURING THE HEALING OF ACETIC ACID-INDUCED ULCER

Ayodeji Folorunsho Ajayi; Busuyi David Kehinde; Olubodun Micheal Lateef; Bolaji Aderibigbe Akorede

doi:10.22159/ajpcr.2018.v11i10.28494

Authors

Ayodeji Folorunsho Ajayi Department of Physiology, LadokeAkintola University of Technology, P.M.B. 4000, Ogbomoso.
Busuyi David Kehinde Department of Biochemistry, Faculty of Basic Medical Sciences, LadokeAkintola University of Technology, Ogbomoso, Nigeria.
Olubodun Micheal Lateef Department of Physiology, LadokeAkintola University of Technology, P.M.B. 4000, Ogbomoso.
Bolaji Aderibigbe Akorede Department of Physiology, LadokeAkintola University of Technology, P.M.B. 4000, Ogbomoso.

DOI:

https://doi.org/10.22159/ajpcr.2018.v11i10.28494

Keywords:

Gastric ulcer healing, Prostaglandin E2, Nitric oxide, Vascular endothelial growth factor

Abstract

Objective: Nitric oxide (NO), prostaglandin E2 (PgE2), and vascular endothelial growth factor (VEGF) are fundamental regulators of epithelial restitution and angiogenesis. They play important roles in ulcer healing. Insights into their possible changes during gastric ulcer healing putting age into consideration could give a guide to the proper management of ulcers in the aging population. This study, therefore, examined alterations in the concentrations of PgE2, NO, and VEGF in the gastric mucosa of rats of different ages after induction of ulcer and during healing.

Methods: Male Wister rats (aged 3, 6, and 18 months old) were divided into three groups according to their ages. The ulcer was induced using the acetic acid ulcer model. Healing indices studied on days 3, 7, and 14 were the macroscopic dimension of ulcer, stomach tissue concentration of PgE2, NO, and VEGF, with the immunohistochemical expression of VEGF.

Results: Outcome of this study showed 100%, 88.36%, and 62.30% area of mucosa healed in 3-, 6-, and 18-month-old rats respectively, on day 14 post-induction of ulcer. PgE2, NO, and VEGF concentrations were inversely proportional to age during healing. Immunohistochemical staining showed that younger rat (3 and 6 months old) had higher expression of VEGF throughout the healing period.

Conclusion: It was therefore concluded that the slower rate of healing in older rats could be due to reduced gastroprotection, epithelial restitution, and angiogenesis as age increases.

Downloads

Download data is not yet available.

Author Biographies

Ayodeji Folorunsho Ajayi, Department of Physiology, LadokeAkintola University of Technology, P.M.B. 4000, Ogbomoso.

Department of Physiology, Senior Lecturer

Busuyi David Kehinde, Department of Biochemistry, Faculty of Basic Medical Sciences, LadokeAkintola University of Technology, Ogbomoso, Nigeria.

Department of Biochemistry, PhD student

Olubodun Micheal Lateef, Department of Physiology, LadokeAkintola University of Technology, P.M.B. 4000, Ogbomoso.

Department of Physiology, Student

Bolaji Aderibigbe Akorede, Department of Physiology, LadokeAkintola University of Technology, P.M.B. 4000, Ogbomoso.

Department of Physiology, Student

References

Geokas MC, Conteas CN, Majumdar AP. The aging gastrointestinal tract, liver, and pancreas. Clin Geriatr Med 1985;1:177-205.

Lee M, Feldman M. Age-related reductions in gastric mucosal prostaglandin levels increase susceptibility to aspirin-induced injury in rats. Gastroenterology 1994;107:1746-50.

Iwamoto J, Saito Y, Honda A, Matsuzaki Y. Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy. World J Gastroenterol 2013;19:1673-82.

Tarnawski AS, Caves TC. Aspirin in the XXI century: Its major clinical impact, novel mechanisms of action, and new safer formulations. Gastroenterology 2004;127:341-3.

Fries JF, Miller SR, Spitz PW, Williams CA, Hubert HB, Bloch DA, et al. Toward an epidemiology of gastropathy associated with nonsteroidal antiinflammatory drug use. Gastroenterology 1989;96:647-55.

Laine L, Takeuchi K, Tarnawski A. Gastric mucosal defense and cytoprotection: Bench to bedside. Gastroenterology 2008;135:41-60.

Tarnawski AS, Ahluwalia A, Jones MK. The mechanisms of gastric mucosal injury: Focus on microvascular endothelium as a key target. Curr Med Chem 2012;19:4-15.

Brzozowski T, Konturek PC, Konturek SJ, Brzozowska I, Pawlik T. Role of prostaglandins in gastroprotection and gastric adaptation. J Physiol Pharmacol 2005;56 Suppl 5:33-55.

Salzman AL, Eaves-Pyles T, Linn SC, Denenberg AG, SzabÃ³ C. Bacterial induction of inducible nitric oxide synthase in cultured human intestinal epithelial cells. Gastroenterology 1998;114:93-102.

Suleyman H, Albayrak A, Bilici M, Cadirci E, Halici Z. Different mechanisms in formation and prevention of indomethacin-induced gastric ulcers. Inflammation 2010;33:224-34.

Morsy MA, Heeba GH, Abdelwahab SA, Rofaeil RR. Protective effects of nebivolol against cold restraint stress-induced gastric ulcer in rats: Role of NO, HO-1, and COX-1,2. Nitric Oxide 2012;27:117-22.

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 1993;239:215-7.

Raji Y, Oloyede GK. Antiulcerogenic effects and possible mechanism of action of Quassia amara (L. Simaroubaceae) extract and its bioactive principles in rats. Afr J Tradit Complement Altern Med 2012;9:112-9.

Tarnawski AS. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 2005;50 Suppl 1:S24-33.

Wallace JL, Devchand PR. Emerging roles for cyclooxygenase-2 in gastrointestinal mucosal defense. Br J Pharmacol 2005;145:275-82.

Wong WM, Playford RJ, Wright NA. Peptide gene expression in gastrointestinal mucosal ulceration: Ordered sequence or redundancy? Gut 2000;46:286-92.

Moraes TM, Rozza AL, Kushima H, Pellizzon CH, Rocha LR, Hiruma-Lima CA, et al. Healing actions of essential oils from Citrus aurantium and d-limonene in the gastric mucosa: The roles of VEGF, PCNA, and COX-2 in cell proliferation. J Med Food 2013;16:1162-7.

Khomeriki SG, Zhukov AG. Morphological features of the gastric mucosa capillary network in patients with portal hypertension. Arkh Patol 2011;73:43-7.

World Medical Association, American Physiological Society. Guiding principles for research involving animals and human beings. Am J Physiol Regul Integr Comp Physiol 2002;283:R281-3.

Ajayi AF, Olaleye SB. Age-related changes in the response of the rat gastric and effect of pentagastrin (PG). Gastroenterology 2015;94:278.

Salami AT, Ndukauba, N.G, Iyiola, TO, Agbola OF, Oluwole FS, Olaleye SB. Gastro protective properties of manganese chloride on acetic acid induced ulcer in wistar rats. Afr J Biomed Res 2014;17:109-17.

Adeniyi OS, Omale J, Egwuje RI, Ajayi OS. Effects of selenium treatment on healing of acetic acid induced gastric ulcer in albino wistar rats. Am J Biomed Res 2016;4:18-22.

Tsikas DJ. Analysis of nitrite and nitrate in biological fluids by assays based on the Griess reaction: appraisal of the Griess reaction in the L-arginine/nitric oxide area of research. J Chromatogr B Analyt Technol Biomed Life Sci 2007;851(1-2):51-70.

Chen M, Hu X. Determination of nitrate in serum by reduction with hydrazine sulfate. J Mod Lab Med 2009;24(5):101-02, 105.

Ogihara Y, Okabe S. Effect and mechanism of sucralfate on healing of acetic acid-induced gastric ulcers in rats. J Physiol Pharmacol 1993;44:109-18.

Gillett C, Fantl V, Smith R, Fisher C, Bartek J, Dickson C, et al. Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res 1994;54:1812-7.

Ruifrok AC, Johnston DA. Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol 2001;23:291-9.

Okabe S, Amagase K. An overview of acetic acid ulcer models-the history and state of the art of peptic ulcer research. Biol Pharm Bull 2005;28:1321-41.

Kang JM, Kim N, Kim J, Oh E, Lee B, Lee BH, et al. Effect of aging on gastric mucosal defence mechanisms: ROS, apoptosis, angiogenesis, and sensory neurons. Am J Physiol Gastrointest Liver Physiol 2010;299:G1147-53.

Brzozowski T. Role of prostaglandins in gastroprotection and gastric adaptation. J Physiol Pharm 2005a;56:33-55.

Ateufack G, Mikwangock DH, Dongmo FB, Yousseu NW, Kamanyi A. Antiulcerogenic and antiulcer activities of Dissotis thollonii (Melasto mataceae) leaves in rats. Int J Pharm Pharm Sci 2015;7:62-9.

Konturek SJ, Konturek PC, Brzozowski T. Prostaglandins and ulcer healing. J Physiol Pharmacol 2005;56 Suppl 5:5-31.

Indal C, Ankita S, Mayank G, Manish KG, Amit S, Raj KG. Gastric antiulcer and ulcer healing effects of Punica granatum L. Peel extract in rats: Role of offensive and defensive mucosal factors and oxidative stress. Int J Pharm Pharm Sci 2017;9:6-11.

GrÃ¸nbech JE, Lacy ER. Role of gastric blood flow in impaired defence and repair of aged rat stomachs. Am J Physiol 1995;269:G737-44.

Wallace JL, Miller MJ. Nitric oxide in mucosal defense: A little goes a long way. Gastroenterology 2000;119:512-20.

deFoneska A, Kaunitz JD. Gastroduodenal mucosal defense. Curr Opin Gastroenterol 2010;26:604-10.

Ferrara N. Vascular endothelial growth factor: Basic science and clinical progress. Endocr Rev 2004;25:581-611.

Majumdar AP, Maitra R, Edgerton EA. Gastric secretion during aging in ratsâ€™ mucosa to acetic acid- and acetic acid-induced ulceration. Arch Bas App Med 1988;3:79-88.