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Vol. 65 No. 3: Issue 3

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The effects of antioxidant combination on indomethacin-induced gastric mucosal injury in rats

https://doi.org/10.14715/cmb/2019.65.3.11
Ismet Burcu Turkyilmaz
Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Istanbul, Turkey
Zeynep Mine Coskun
Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Istanbul Bilim University, Istanbul, Turkey
Sema Bolkent
Department of Medical Biology, Faculty of Cerrahpasa Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
Refiye Yanardag
Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Istanbul, Turkey

Corresponding Author(s) : Ismet Burcu Turkyilmaz

burcut@istanbul.edu.tr

Cellular and Molecular Biology, Vol. 65 No. 3: Issue 3

Abstract

The aim of this study is an investigation the protective effects of vitamin C (Vit C), vitamin E (Vit E), β-carotene, sodium selenate combination in indomethacin-induced gastric mucosal damage in rats. Rats were divided into 6 groups. Group I: Intact animals (control). Group II: Control animals receiving Vit C (100 mg/kg/day), Vit E (100 mg/kg/day), β-carotene (15 mg/kg/day) and sodium selenate (0.2 mg/kg/day) for 3 days. Group III: Animals receiving 25 mg/kg indomethacin. Group IV: Animals receiving Vit C, Vit E, β-carotene and sodium selenate (in same doses) for 3 days 2 h before the administration of indomethacin. Group V: Animals receiving ranitidine (150 mg/kg) for 3 days. Group VI: Animals receiving ranitidine for 3 days 2 h before to the administration of indomethacin (in same dose and time). The administration of indomethacin caused a decrease in the levels of glutathione, mucus, hexosamine and in the activities of glutathione-S-transferase, sodium-potassium ATPase, thromboplastic activity and an increase in the aspartate and alanine amino transferase, alkaline phosphatase, catalase, lactate dehydrogenase, myeloperoxidase activities and sialic acid, lipid peroxidation and protein carbonyl levels.  Stomach caspase-8 immun+ cell numbers showed a slight increase while caspase-9 immun+ cell numbers reduced in indomethacin given group compared to control animals. Our results findings suggest that the combination of Vit C, Vit E, β-carotene, sodium selenate and ranitidine has a protective effect on indomethacin-induced gastric mucosal injury of rats.

Keywords

Stomach Antioxidant Indomethacin Oxidative stress Apoptosis.
Turkyilmaz, I. B., Coskun, Z. M., Bolkent, S., & Yanardag, R. (2019). The effects of antioxidant combination on indomethacin-induced gastric mucosal injury in rats. Cellular and Molecular Biology, 65(3), 76–83. https://doi.org/10.14715/cmb/2019.65.3.11
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References
  1. Ozbakis-Dengiz G, Hekimoglu A, Kandemir N, Kurcer Z. Effects of statins in an indomethacin-induced gastric injury model in rats. Turk J Gastroenterol 2012; 23:456-62.
  2. Radulovic NS, Jovanovic I, Ilic IR, Randjelović PJ, Stojanović NM, Miltojević AB. Methyl and isopropyl N-methylanthranilates attenuate diclofenac- and ethanol-induced gastric lesions in rats. Life Sci 2013; 93:840-46.
  3. Eleawa S, Bin-Jaliah I, Alkhateeb M, Bayoumy NM, Alessa R, Sakr HF. The impact of dehydroepiandrostreone on indomethacin-induced gastric lesions in rats. Acta Physiol Hung 2014; 101:77-87.
  4. Zhu D, Tong Q, Liu W, Tian M, Xie W, Ji L, et al. Angiotensin (1-7) protects against stress-induced gastric lesions in rats. Biochem Pharmacol 2014; 87:467-76.
  5. Nagano Y, Matsui H, Tamura M, Shimokawa O, Nakamura Y, Kaneko T, et al. NSAIDs and acidic environment induce gastric mucosal cellular mitochondrial dysfunction. Digestion 2012; 85:131-35.
  6. Park JM, Han YM, Kangwan N, Lee SY, Jung MK, Kim EH, et al. S-allyl cysteine alleviates nonsteroidal anti-inflammatory drug-induced gastric mucosal damages by increasing cyclooxygenase-2 inhibition, heme oxygenase-1 induction, and histone deacetylation inhibition. J Gastroenterol Hepatol 2014; 29:80-92.
  7. Suleyman H, Demircan B, Karagoz Y. Anti-inflammatory and side effects of cyclooxgenase inhibitors. Pharmacol Res 2007; 59:247-58.
  8. Naito Y, Kurroda M, Mizushima K, Takagi T, Handa O, Kokura S, et al. Transcriptome analysis for cytoprotective actions of Rebamipide against indomethacin-induced gastric mucosal injury in rats. J Clin Biochem Nutr 2007; 41:202-10.
  9. Andrews FJ, Malcontenti-Wilson C, O'Brien PE. Effect of nonsteroidal anti-inflammatory drugs on LFA-1 and ICAM-1 expression in gastric mucosa. Am J Physiol 1994; 266:G657–64.
  10. Albayrak F, Odabasoglu F, Halici Z, Polat B, Dursun H, Uyanik A, et al. The role of erythropoietin in the protection of gastric mucosa from indomethacin-induced injury and its relationship with oxidant and antioxidant parameters in rats. J Pharm Pharmacol 2010; 62:85-90.
  11. Jung J, Nam Y, Sohn UD. Inhibitory effects of ECQ on indomethacin-induced gastric damage in rats. Korean J Physiol Pharmacol 2012; 16:399-404.
  12. Mates JM, Perez-Gomez C, Nudez de Castro I. Antioxidant enzymes and human diseases. Clin Biochem 1999; 32:595-603.
  13. Yanardag R, Ozsoy-Sacan O, Ozdil S, Bolkent S. Combined effects of vitamin C, vitamin E, and sodium selenate supplementation on absolute ethanol-induced injury in various organs of rats. Int J Tox 2007; 26:513-23.
  14. Mohanta RK, Garg AK, Dass RS. Effect of vitamin E supplementation on arsenic induced in blood biochemical profile, oxidant/antioxidant status, serum cortisol level and retention of arsenic and selenium in goats. J Trace Elem Med Biol 2015; 29:188-94.
  15. Jang SH, Lim JW, Kim H. Beta-carotene inhibits Helicobacter pylori-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in human gastric epithelial AGS cells. J Physiol Pharmacol 2009; 60:131-37.
  16. Kim JH, Park SH, Nam SW, Choi YH. Gastroprotective effect of selenium on ethanol-induced gastric damage in rats. Int J Mol Sci 2012; 13:5740-50.
  17. Kamble P, Mohsin N, Jha A, Date A, Upadhaya A, Mohammad E, et al. Selenium intoxication with selenite broth resulting in acute renal failure and severe gastritis. Saudi J Kidney Dis Transpl 2009; 20:106-11.
  18. Chandranath SI, Bastaki SM, D'Souza A, Adem A, Singh J. Attenuation of stress-induced gastric lesions by lansoprazole, PD-136450 and ranitidine in rats. Mol Cell Biochem 2011; 349:205-12.
  19. McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol 2013; 5:a008656.
  20. Li J and Yuan J. Caspases in apoptosis and beyond. Oncogene 2008; 27:6194–6206.
  21. Koc M, Imik H, Odabasoglu F. Gastroprotective effect and anti-oxidative properties of ascorbic acid on indomethacin-induced gastric injuries in rats. Biol Trace Elem Res 2008; 126:222-36.
  22. Beutler E, Duran O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963; 61:882-88.
  23. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957; 28:56-63.
  24. Walter K and Schutt C. Acid and alkaline phosphatase in serum (Two point method). In: Bergmeyer, H.U. (Ed.), Methods of Enzymatic Analysis, vol. 2. Verlag Chemie GmbH, Florida, 1974, pp. 856– 60.
  25. Corne SJ, Morrissey SM, Woods RJ. A method for the quantitative estimation of gastric barrier mucus. J Physiol 1974; 242:116- 17.
  26. Winzler RJ. Determination of serum glycoproteins. In: Methods of Biochemical Analysis, Glick, DP, ed. New York: Interscience Publishers Inc, 1955, pp. 279-311.
  27. Lorentz K, Weiss T, Kraas E. Sialic acid in human serum and cerebrospinal fluid. J Clin Chem Clin Biochem 1986; 24:189-98.
  28. Ingram GIC and Hills M. Reference method for the one stage prothrombin time test on human blood. Thromb Haemost 1976; 36:237-38.
  29. Beutler E. Glutathione in red cell metabolism a manual of biochemical methods. 2nd ed. New York, Grune and Stratton. 1975, pp. 112-14.
  30. Ledwozyw A, Michalak J, Stepien A, Kadziołka A. The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atheroschlerosis. Clin Chim Acta 1986; 155:275-83.
  31. Lowry OH, Rosebrough HJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193:265-75.
  32. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 1990; 186:464-78.
  33. Aebi H. Catalase in vitro. Methods Enzymol 1984; 105:121-26.
  34. Habig WH and Jacoby WB. Assays for differentiation of glutathione-S-transferases. Methods Enzymol 1981; 77:398-405.
  35. Bais R and Philcox M. Approved recommendation on IFCC methods for the measurement of catalytic concentration of enzymes. Part 8. IFCC method for lactate dehydrogenase (I-Lactate: NAD+Oxidoreductase, EC 1.1.1.27). International Federation of Clinical Chemistry (IFCC). Eur J Clin Chem Clin 1994; 32:639-55.
  36. Ridderstap AS and Bonting SL. Na+- K+-activated ATPase and exocrine pancreatic secretion in vitro. Am J Physiol 1969; 217:1721-27.
  37. Wei H and Frenkel K. In vivo formation of oxidized DNA bases in tumor promoter-treated mouse skin. Cancer Res 1991; 51:4443-49.
  38. Heeba GH, Hassan MKA, Amin RS. Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: Role of nitric oxide and prostaglandins. Eur J Pharmacol 2009; 607:188-93.
  39. Regula J, Butruk E, Dekkers CP, de Boer SY, Raps D, Simon L, et al. Prevention of NSAID-associated gastrointestinal lesions: a comparison study pantoprazole versus omeprazole. Am J Gastroenterol 2006; 101:1747–55.
  40. Yeomans ND, Tulassay Z, Juhasz L, Rácz I, Howard JM, van Rensburg CJ, et al. A comparison o omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. New Eng J Med 1998; 338:719–26.
  41. Hippisley-Cox J, Coupland C, Logan R. Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional nonsteroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ 2005; 331:1310-16.
  42. Berenguer B, Trabadela C, Sánchez-Fidalgo S, Quí­lez A, Miño P, De la Puerta R, et al. The aerial parts of Guazuma ulmifolia Lam. protect against NSAID-induced gastric lesions. J Ethnopharmacol 2007; 114:153-60.
  43. Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology 2008; 245:194–205.
  44. Repetto MG and Llesuy SF. Antioxidant properties of natural compounds used in popular medicine for gastric ulcers. Braz J Med Biol Res 2002; 35:523–34.
  45. Seno K, Joh T, Yokoyama Y, Itoh M. Role of mucus in gastric mucosal injury induced by local ischemia/reperfusion. J Lab Clin Med 1995; 126:287–93.
  46. Laurence DR and Bennet PN. Clinical Pharmacology, 7th edn. Churchill, Livingstone, New York, 1992, pp. 300–51.
  47. Ninomiya K, Kitano S, Yoshida T, Bandoh T, Baatar D, Tsuboi S. Impaired adaptive cytoprotection to ethanol-induced damage in gastric mucosa of portal hypertensive rats. Dig Dis Sci 1999; 44:1254-60.
  48. Varki A. Sialic acids as ligands in recognition phenomena. FASEB J 1997; 11:248–55.
  49. Naito Y, Yoshikawa T, Matsuyama K, Nishimura S, Yagi N, Kondo M. Effects of free radical scavengers on indomethacin-induced aggravation of gastric ulcer in rats. Dig Dis Sci 1995; 40:2019-21.
  50. Elliot SN and Wallace JL. Neutrophil-mediated gastrointestinal injury. Can J Gastroenterol 1998; 12:559–68.
  51. Miura T, Muraoka S, Fujimoto Y. Lipid peroxidation induced by indomethacin with horseradish peroxidase and hydrogen peroxide: Involvement of indomethacin radicals. Biochem Pharmacol 2002; 63:2069-74.
  52. Ahmadi A, Ebrahimzadeh MA, Ahmad-Ashrafi S, Karami M, Mahdavi MR, Saravi SS. Hepatoprotective, antinociceptive and antioxidant activities of cimetidine, ranitidine and famotidine as histamine H2 receptor antagonists. Fundam Clin Pharmacol 2011; 25:72-9.
  53. Banerjee D, Bauri AK, Guha RK, Bandyopadhyay SK, Chattopadhyay S. Healing properties of malabaricone B and malabaricone C against indomethacin-induced gastric ulceration and mechanism of action. Eur J Pharmacol 2008; 578:300-12.
  54. Beal MF. Oxidatively modified proteins in aging and disease. Free Rad Biol Med 2002; 32:797–803.
  55. Suleyman H, Cadirci E, Albayrak A, Polat B, Halici Z, Koc F. Comparative study on the gastroprotective potential of some antidepressants in indomethacin-induced ulcer in rats. Chem Biol Interact 2009; 180:318-24.
  56. Banerjee RK. Non-steroidal anti-inflammatory drugs inhibit gastric peroxidase activity. Biochim Biophys Acta 1990; 1034:275–79.
  57. Aperia A. New roles for an old enzyme: Na,K-ATPase emerges as an interesting drug target. J Intern Med 2007; 261:44-52.
  58. Van Zyl JM, Kriegler A, van Der Walt BJ. Anti-oxidant properties of H2-receptor antagonists effects on myeloperoxidase-catalysed reactions and hydroxyl radical generation in a ferrous-hydrogen peroxide system. Biochem Pharmacol 1993; 45:2389–97.
  59. Totzke G, Schulze-Osthoff K, Jänicke RU. Cyclooxygenase-2 (COX-2) inhibitors sensitize tumor cells specifically to death receptor-induced apoptosis independently of COX-2 inhibition. Oncogene 2003; 22:8021–30.
  60. Wallace JL, McKnight W, Reuter BK, Vergnolle N. NSAID-induced gastric damage in rats. Requirement for inhibition of both cyclooxygenase 1 and 2. Gastroenterology 2000; 119:706-14.
  61. Monie TP and Bryant CE. Caspase-8 functions as a key mediator of inflammation and pro-IL-1β processing via both canonical and non-canonical pathways. Immunol Rev 2015; 265:181-93.
  62. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994; 107:1183-88.
  63. Ristimäki A, Honkanen N, Jänkälä H, Sipponen P, Härkönen M. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 1997; 57:1276-80.
  64. Tucker ON, Dannenberg AJ, Yang EK, Zhang F, Teng L, Daly JM, et al. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res 1999; 59:987-90.
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