Gastroprotective effects of hydrogen sulfide, carbon monoxide and nitric oxide on an experimental ulcer model in rats

Abstract

Background/Aim: Gastric mucosal injury induced by several agents such as ethanol, stress or nonsteroidal anti-inflammatory drugs (NSAIDs) is a common severe disorder. Hydrogen sulfide (H2S), carbon monoxide (CO) and nitric oxide (NO) are gaseous autacoids that are endogenously produced in mammalian tissues. Recently, several studies confirmed that H2S, CO and NO play a role in gastroprotection. Our work aimed to evaluate and compared the gastroprotective effects of H2S, CO and NO on ethanol-, indomethacin- and stress-induced rat ulcer models. Methods: The effects of NaHS (5 mg/kg), CORM-2 (5 mg/kg) and L-arginine (100 mg/kg) were investigated on gastric ulcer models induced by ethanol (1 ml 96% i.g.), stress (cold+immobility) and indomethacin (40 mg/kg i.g.). The ulcer index, gastric mucus secretion, free and total acidity, and levels of TNF-α, PGE2, MDA GSH, COX-1, COX-2 were measured. Results: NaHS and CORM-2 decreased the increased TNF-α and MDA levels in ethanol-induced ulcer. L-arginine reduced mucin secretion, TNF-α and GSH levels in stress-induced gastric ulcer. Conclusion: The present study showed that H2S and CO may have gastroprotective activity against ethanol-induced ulcers and NO may be gastroprotective against stress-induced ulcers.

Keywords

• Gasotransmitters
• Hydrogen sulfide
• Carbon monoxide
• Nitric oxide
• Ulcer

Hidrojen sülfür, karbon monoksit ve nitrik oksidin sıçanlarda deneysel ülser modelleri üzerindeki gastroprotektif etkileri

Öz

Giriş / Amaç: Mide mukozal hasarı, etanol, stres veya nonsteroid antiinflamatuvar ilaçlar (NSAID'ler) gibi çeşitli ajanların neden olduğu yaygın görülen ciddi bir hastalıktır. Hidrojen sülfür (H2S), karbon monoksit (CO) ve nitrik oksit (NO), memeli dokularında endojen olarak üretilen gaz halindeki otakoidlerdir. Son zamanlarda birkaç çalışma, H2S, CO ve NO'nun gastroproteksiyonda rol oynadığını doğrulamıştır. Çalışmamız, H2S, CO ve NO'nun etanol, indometazin ve stres kaynaklı sıçan ülseri modelleri üzerindeki gastroprotektif etkilerini değerlendirmeyi ve karşılaştırmayı amaçlamıştır. Yöntemler: NaHS (5 mg/kg), CORM-2 (5 mg/kg) ve L-argininin (100 mg/kg) etkileri, etanol (1 ml% 96 ​​i.g), stres (soğuk + hareketsizlik) ve indometasin (40 mg/kg, i.g) ile indüklenen mide ülseri modellerinde araştırılmıştır. . Ülser indeksi, mide mukus sekresyonu, serbest ve toplam asidite, TNF-α, PGE2, MDA GSH, COX-1, COX-2 seviyeleri ölçülmüştür. Bulgular: H2S ve CO'nun etanol ile indüklenen ülsere karşı ve NO'nun stres kaynaklı ülsere karşı koruyucu etkileri olduğu tespit edilmiştir. Sonuç: Bu çalışma, H2S ve CO'nun etanol kaynaklı ülserlere ve NO'nun strese bağlı ülserlere karşı koruyucu aktiviteye sahip olabileceğini göstermiştir.

Anahtar Kelimeler

• gaz transmitterler
• hidrojen sülfür
• nitrik oksit
• karbon monoksit

Kaynakça

1. 1. Kuna L, Jakab J, Smolic R, Raguz-Lucic N, Vcev A, Smolic M. Peptic Ulcer Disease: A Brief Review of Conventional Therapy and Herbal Treatment Options. J Clin Med. 2019;8(2).
2. 2. Kangwan N, Park JM, Kim EH, Hahm KB. Quality of healing of gastric ulcers: Natural products beyond acid suppression. World J Gastrointest Pathophysiol. 2014;5(1):40-7.
3. 3. Ribeiro AR, do Nascimento Valenca JD, da Silva Santos J, Boeing T, da Silva LM, de Andrade SF, et al. The effects of baicalein on gastric mucosal ulcerations in mice: Protective pathways and anti-secretory mechanisms. Chem Biol Interact. 2016;260:33-41.
4. 4. Adinortey MB AC, Galyuon I, Nyarko A. In Vivo Models Used for Evaluation of Potential Antigastroduodenal Ulcer Agents. Ulcers. 2013;2013:12.
5. 5. Arab HH, Salama SA, Omar HA, Arafa el SA, Maghrabi IA. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions. PLoS One. 2015;10(3):e0122417.
6. 6. Alqasoumi S, Al-Sohaibani M, Al-Howiriny T, Al-Yahya M, Rafatullah S. Rocket "Eruca sativa": a salad herb with potential gastric anti-ulcer activity. World J Gastroenterol. 2009;15(16):1958-65.
7. 7. Matsui H, Shimokawa O, Kaneko T, Nagano Y, Rai K, Hyodo I. The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. J Clin Biochem Nutr. 2011;48(2):107-11.
8. 8. Beck PL, Xavier R, Lu N, Nanda NN, Dinauer M, Podolsky DK, et al. Mechanisms of NSAID-induced gastrointestinal injury defined using mutant mice. Gastroenterology. 2000;119(3):699-705.

9. 9. Allen A, Flemstrom G. Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am J Physiol Cell Physiol. 2005;288(1):C1-19.
10. 10. Levenstein S, Kaplan GA, Smith M. Sociodemographic characteristics, life stressors, and peptic ulcer. A prospective study. J Clin Gastroenterol. 1995;21(3):185-92.
11. 11. Govindarajan R, Vijayakumar M, Singh M, Rao Ch V, Shirwaikar A, Rawat AK, et al. Antiulcer and antimicrobial activity of Anogeissus latifolia. J Ethnopharmacol. 2006;106(1):57-61.
12. 12. Das D, Banerjee RK. Effect of stress on the antioxidant enzymes and gastric ulceration. Mol Cell Biochem. 1993;125(2):115-25.
13. 13. Farrugia G, Szurszewski JH. Carbon monoxide, hydrogen sulfide, and nitric oxide as signaling molecules in the gastrointestinal tract. Gastroenterology. 2014;147(2):303-13.
14. 14. Magierowska K, Magierowski M, Hubalewska-Mazgaj M, Adamski J, Surmiak M, Sliwowski Z, et al. Carbon Monoxide (CO) Released from Tricarbonyldichlororuthenium (II) Dimer (CORM-2) in Gastroprotection against Experimental Ethanol-Induced Gastric Damage. PLoS One. 2015;10(10):e0140493.
15. 15. Mard SA, Neisi N, Solgi G, Hassanpour M, Darbor M, Maleki M. Gastroprotective effect of NaHS against mucosal lesions induced by ischemia-reperfusion injury in rat. Dig Dis Sci. 2012;57(6):1496-503.
16. 16. Brzozowski T, Konturek PC, Drozdowicz D, Konturek SJ, Zayachivska O, Pajdo R, et al. Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways. World J Gastroenterol. 2005;11(41):6450-8.
17. 17. Velazquez-Moyado JA, Martinez-Gonzalez A, Linares E, Bye R, Mata R, Navarrete A. Gastroprotective effect of diligustilide isolated from roots of Ligusticum porteri coulter & rose (Apiaceae) on ethanol-induced lesions in rats. J Ethnopharmacol. 2015;174:403-9.
18. 18. Senay EC, Levine RJ. Synergism between cold and restraint for rapid production of stress ulcers in rats. Proc Soc Exp Biol Med. 1967;124(4):1221-3.
19. 19. Kianbakht S MK. Effects of Saffron and its Active Constituents, Crocin and Safranal, on Prevention of Indomethacin Induced Gastric Ulcers in Diabetic and Nondiabetic Rats. J Med Plants. 2009;1(29 And S5):30-8.
20. 20. Yildirim E, Sagiroglu O, Kilic FS, Erol K. Effects of nabumetone and dipyrone on experimentally induced gastric ulcers in rats. Inflammation. 2013;36(2):476-81.
21. 21. Guth PH, Aures D, Paulsen G. Topical aspirin plus HCl gastric lesions in the rat. Cytoprotective effect of prostaglandin, cimetidine, and probanthine. Gastroenterology. 1979;76(1):88-93.
22. 22. Batu OS, Erol K. The effects of some nonsteroidal anti-inflammatory drugs on experimental induced gastric ulcers in rats. Inflammopharmacology. 2007;15(6):260-5.
23. 23. Corne SJ, Morrissey SM, Woods RJ. Proceedings: A method for the quantitative estimation of gastric barrier mucus. J Physiol. 1974;242(2):116P-7P.
24. 24. Chatterjee M, Saluja R, Kanneganti S, Chinta S, Dikshit M. Biochemical and molecular evaluation of neutrophil NOS in spontaneously hypertensive rats. Cell Mol Biol (Noisy-le-grand). 2007;53(1):84-93.
25. 25. Almasaudi SB AA, Al-Hindi RR, El-Shitany NA, Abdel-Dayem UA, Ali SS, Saleh RM, et al. Manuka Honey Exerts Antioxidant and Anti-Inflammatory Activities That Promote Healing of Acetic Acid-Induced Gastric Ulcer in Rats. Evidence-Based Complementary and Alternative Medicine. 2017;2017.
26. 26. Niv Y, Banic M. Gastric barrier function and toxic damage. Dig Dis. 2014;32(3):235-42.
27. 27. Hajrezaie M, Golbabapour S, Hassandarvish P, Gwaram NS, AH AH, Mohd Ali H, et al. Acute toxicity and gastroprotection studies of a new schiff base derived copper (II) complex against ethanol-induced acute gastric lesions in rats. PLoS One. 2012;7(12):e51537.
28. 28. Li Q, Hu X, Xuan Y, Ying J, Fei Y, Rong J, et al. Kaempferol protects ethanol-induced gastric ulcers in mice via pro-inflammatory cytokines and NO. Acta Biochim Biophys Sin (Shanghai). 2018;50(3):246-53.
29. 29. Chavez-Pina AE, Tapia-Alvarez GR, Navarrete A. Inhibition of endogenous hydrogen sulfide synthesis by PAG protects against ethanol-induced gastric damage in the rat. Eur J Pharmacol. 2010;630(1-3):131-6.
30. 30. Liu L, Cui J, Song CJ, Bian JS, Sparatore A, Soldato PD, et al. H(2)S-releasing aspirin protects against aspirin-induced gastric injury via reducing oxidative stress. PLoS One. 2012;7(9):e46301.
31. 31. Vandiver M, Snyder SH. Hydrogen sulfide: a gasotransmitter of clinical relevance. J Mol Med (Berl). 2012;90(3):255-63.
32. 32. Medeiros JV, Bezerra VH, Gomes AS, Barbosa AL, Lima-Junior RC, Soares PM, et al. Hydrogen sulfide prevents ethanol-induced gastric damage in mice: role of ATP-sensitive potassium channels and capsaicin-sensitive primary afferent neurons. J Pharmacol Exp Ther. 2009;330(3):764-70.
33. 33. Vendramini-Costa DB, Monteiro KM, Iwamoto LH, Jorge MP, Tinti SV, Pilli RA, et al. Gastroprotective effects of goniothalamin against ethanol and indomethacin-induced gastric lesions in rats: Role of prostaglandins, nitric oxide and sulfhydryl compounds. Chem Biol Interact. 2014;224:206-12.
34. 34. Moustafa A, Habara Y. Hydrogen sulfide regulates Ca(2+) homeostasis mediated by concomitantly produced nitric oxide via a novel synergistic pathway in exocrine pancreas. Antioxid Redox Signal. 2014;20(5):747-58.
35. 35. Konturek SJ. Mechanisms of gastroprotection. Scand J Gastroenterol Suppl. 1990;174:15-28.
36. 36. Pawlik M, Pajdo R, Kwiecien S, Ptak-Belowska A, Sliwowski Z, Mazurkiewicz-Janik M, et al. Nitric oxide (NO)-releasing aspirin exhibits a potent esophagoprotection in experimental model of acute reflux esophagitis. Role of nitric oxide and proinflammatory cytokines. J Physiol Pharmacol. 2011;62(1):75-86.
37. 37. Czekaj R, Majka J, Ptak-Belowska A, Szlachcic A, Targosz A, Magierowska K, et al. Role of curcumin in protection of gastric mucosa against stress-induced gastric mucosal damage. Involvement of hypoacidity, vasoactive mediators and sensory neuropeptides. J Physiol Pharmacol. 2016;67(2):261-75.
38. 38. Andreadou I, Iliodromitis EK, Rassaf T, Schulz R, Papapetropoulos A, Ferdinandy P. The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning. Br J Pharmacol. 2015;172(6):1587-606.
39. 39. Takagi T, Uchiyama K, Naito Y. The therapeutic potential of carbon monoxide for inflammatory bowel disease. Digestion. 2015;91(1):13-8.
40. 40. Magierowski M, Magierowska K, Szmyd J, Surmiak M, Sliwowski Z, Kwiecien S, et al. Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised by Mild Stress Against Alendronate Injury. Dig Dis Sci. 2016;61(11):3176-89.
41. 41. Takeuchi K, Ohuchi T, Okabe S. Endogenous nitric oxide in gastric alkaline response in the rat stomach after damage. Gastroenterology. 1994;106(2):367-74.
42. 42. Lopez-Belmonte J, Whittle BJ, Moncada S. The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa. Br J Pharmacol. 1993;108(1):73-8.
43. 43. Andrews FJ, Malcontenti-Wilson C, O'Brien PE. Protection against gastric ischemia-reperfusion injury by nitric oxide generators. Dig Dis Sci. 1994;39(2):366-73.
44. 44. Ribbons KA, Zhang XJ, Thompson JH, Greenberg SS, Moore WM, Kornmeier CM, et al. Potential role of nitric oxide in a model of chronic colitis in rhesus macaques. Gastroenterology. 1995;108(3):705-11.
45. 45. Wei Q, Korejo NA, Jiang J, Xu M, Zheng K, Mao D, et al. Mitigation of stress from gastric mucosal injuries by mulberry extract may occur via nitric oxide synthase signaling in mice. Tissue Cell. 2018;54:59-64.
46. 46. Park CH, Son HU, Son M, Lee SH. Protective effect of Acer mono Max. sap on water immersion restraint stress-induced gastric ulceration. Exp Ther Med. 2011;2(5):843-8.