Nikotinin Sıçan Pankreatit Modelindeki Hafifletici Etkisinde Vagusun Rolünün Araştırılması

Meltem Kolgazi; Zozan Güleken; Bircan Kolbaşı; Canberk Sami Başıbüyük; Feriha Ercan; Berrak Yeğen

doi:10.31067/acusaglik.849995

Research Article

Nikotinin Sıçan Pankreatit Modelindeki Hafifletici Etkisinde Vagusun Rolünün Araştırılması

Year 2021, , 166 - 175, 01.04.2021

Meltem Kolgazi Zozan Güleken , Bircan Kolbaşı , Canberk Sami Başıbüyük Feriha Ercan , Berrak Yeğen

https://doi.org/10.31067/acusaglik.849995

Abstract

Nikotininbirçok farklı dokuda anti-inflamatuvar etkilere sahip olduğu ve bu etkileri kolinerjik anti-inflamatuvar yolağı aktive ederek gerçekleştirdiği gösterilmiştir. Çalışmada akut pankreatit modelinde nikotin tedavisinin etkilerini ve bu etkilerin kolinerjik yolla ilişkisini araştırmak amaçlanmıştır. Wistar albino sıçanların pankreas-safra ortak kanalı bağlanırken(PSKB),bir grubada yalancı-cerrahi (YC)uygulandı. PSKB sıçanlaravagal aferent denervasyon(perivagal kapsaisin; 10mg/ml)veya trunkal vagotomi uygulandı ya da vagusları sağlam bırakıldı. PSKB grupları cerrahi sonrası ikiye ayrılarak 4 gün boyunca intraperitoneal nikotin (1 mg/kg/gün) ya da serum fizyolojik verildi. Dördüncü günde dekapitasyonu takiben,serumda tümör nekroz faktör (TNF)- ve interlökin (IL)-10 ölçümü, akciğer, karaciğer ve pankreas dokularındamiyeloperoksidaz aktivitesi (MPO), malondialdehit (MDA), glutatyon (GSH) ölçümleri ve histolojik inceleme yapıldı. TNF- düzeyi PSKB grubunda YC grubuna göre belirgin şekilde daha yüksekken, nikotin tedavisi alanlarda belirgin şekilde daha düşüktü. IL-10 düzeyi ise SF tedavisi almış PSKB grubunda YC grubuna göre daha düşüktü ve nikotin tedavisi ile arttığı gözlendi.YC grubuna göre PSKB grubunun pankreas, karaciğer ve akciğer dokularında mikroskopik hasar, MDA, MPO düzeyleri artarken GSH düzeyleri azaldı. Nikotin tedavisi ile karaciğer ve pankreas dokularındaki hasar, MDA, MPO düzeyleri azaldı ve GSH miktarları korundu. Vagal aferent denervasyon ya da trunkal vagotomi yapılması nikotinin bu koruyucu etkilerini değiştirmedi. Sonuçlar, nikotininpankreatit hasarına karşıkoruyucu etkilerini vagal yoldan bağımsız olarak, doğrudan immün hücreler üzerindeki 7nAChR aktivasyonu ile nötrofil infiltrasyonunu ve pro-inflamatuvar sitokinleri inhibe ederek gerçekleştirdiğini ortaya koymaktadır.

Keywords

pankreatit, nikotin, vagus, inflamasyon, pankreatik kanal bağlama

References

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8. Danson SJ, Rowland C, Rowe R, Ellis S, Crabtree C, Horsman JM, et al. The relationship between smoking and quality of life in advanced lung cancer patients: a prospective longitudinal study. Support Care Cancer. 2016; 24(4):1507-16.
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29. Mazelin L, Theodorou V, More J, Fioramonti J, Bueno L. Protective role of vagal afferents in experimentally-induced colitis in rats.J Auton Nerv Syst 1998;73:38–45.
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33. Casini A, Ferrali M, Pompella AS, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene intoxicated mice. Am J Pathol. 1986; 123: 520-531
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Investigation of The Role of Vagus in The Ameliorative Effect of Nicotine on Rat Pancreatitis Model

Year 2021, , 166 - 175, 01.04.2021

Meltem Kolgazi Zozan Güleken , Bircan Kolbaşı , Canberk Sami Başıbüyük Feriha Ercan , Berrak Yeğen

https://doi.org/10.31067/acusaglik.849995

Abstract

The anti-inflammatory effects of nicotine on various organs and the involvement of the cholinergic anti-inflammatory pathway activation in these effects were previously shown. The purpose of the study is to evaluate the effects of nicotine treatment on acute pancreatitis model and to investigate the association of cholinergic pathway with these effects.In Wistar albino rats common pancreatic-biliaryduct was ligated (PBDL) or sham-operation were performed. In PBDL rats, vagal afferent denervation (perivagal capsaicin; 10mg/ml) or truncal vagotomy was appliedor the vagi were left intact. Postoperatively, PBDL groups were treated intraperitoneally with either nicotine (1 mg/kg/day) or saline for 4 days. Following decapitation on the 4th day, serum tumor necrosis factor (TNF)-and interleukin (IL)-10 levels andmyeloperoxidase activity (MPO), malondialdehiyde (MDA) and glutathione (GSH) levels in the pancreas, liver and lung tissues were measured, and histopathological analyses were made. While the TNF-α level was significantly higher in the PBDL group than in the YC group, it was significantly lower in the subjects takennicotine treatment. IL-10 level was lower in the PBDL group treated with saline than in the YC group and an increase was observed with nicotine treatment.Compared to sham-operated group, microscopic damage scores, MDA, MPO levels in the pancreas, liver and lung tissues of the PBDL group were elevated, while GSH levels were reduced. Nicotine treatment depressed MDA and MPO levels,preserved GSH contents and reduced histological damage in the pancreas and liver. Vagal afferent denervation or truncal vagotomy did not alter these protective effects of nicotine. The results suggest that the protective effects of nicotine on pancreatic inflammation could occur independently of the vagal pathways, but directly by the activation of 7nAChR on the immune cells and by inhibiting neutrophil infiltration and pro-inflammatory cytokine release.

Keywords

pancreatitis, nicotine, vagus, inflammation, pancreatic duct ligation

References

1. Greenberg JA, Hsu J, Bawazeer M, Marshall J, Friedrich JO, Nathens A, et al. Clinical practice guideline: management of acute pancreatitis. Can J Surg. 2016; 59(2):128-40.
2. Wang GJ, Li Y, Zhou ZG, Wang C, Meng WJ. Integrity of the pancreatic duct-acinar system in the pathogenesis of acute pancreatitis. Hepatobiliary Pancreat Dis Int. 2010; 9(3):242-7.
3. Hegyi P, Pandol S, Venglovecz V, Rakonczay Z Jr. The acinar-ductal tango in the pathogenesis of acute pancreatitis. Gut. 2011; 60(4):544-52.
4. Mooren FCh, Hlouschek V, Finkes T, Turi S, Weber IA, Singh J, et al. Early changes in pancreatic acinar cell calcium signaling after pancreatic duct obstruction. J Biol Chem. 2003; 278(11):9361-9.
5. Abdulla A, Awla D, Thorlacius H, Regnér S. Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis. J Leukoc Biol. 2011; 90(5):975-82.
6. Kasımay O, Işeri SO, Barlas A, Bangir D, Yeğen C, Arbak S, Yeğen BC. Ghrelin ameliorates pancreaticobiliary inflammation and associated remote organ injury in rats. Hepatol Res. 2006; 36(1):11-9.
7. Barlas A, Cevik H, Arbak S, Bangir D, Sener G, Yeğen C, Yeğen BC.Melatonin protects against pancreaticobiliary inflammation and associated remote organ injury in rats: role of neutrophils. J Pineal Res. 2004; 37(4):267-75.
8. Danson SJ, Rowland C, Rowe R, Ellis S, Crabtree C, Horsman JM, et al. The relationship between smoking and quality of life in advanced lung cancer patients: a prospective longitudinal study. Support Care Cancer. 2016; 24(4):1507-16.
9. Doll R, Peto R. Mortality in relation to smoking: 20 years' observations on male British doctors. Br Med J 1976; 2:1525-1536.
10. Fratiglioni L, Wang HX. Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological studies. Behav Brain Res 2000;113:117-120.
11. Manthorpe R, Benoni C, Jacobsson L, Kirtava Z, Larsson A, Liedholm R, et al. Lower frequency of focal lip sialadenitis (focus score) in smoking patients. Can tobacco diminish the salivary gland involvement as judged by histological examination and anti-SSA/Ro and anti-SSB/La antibodies in Sjogren's syndrome? Ann Rheum Dis 2000;59:54-6
12. Sopori M. Effects of cigarette smoke on the immune system. Nat Rev Immunol 2002; 2:372-377.
13. Rezonzew G, Chumley P, Feng W, Hua P, Siegal GP, Jaimes EA. Nicotine exposure and the progression of chronic kidney disease: role of the alpha7-nicotinic acetylcholine receptor. Am J Physiol Renal Physiol 2012;303:F304-F312
14. Bruin JE, Petre MA, Lehman MA et al. Maternal nicotine exposure increases oxidative stress in the offspring. Free Radic Biol Med 2008;44:1919-1925
15. Bryden DW, Burton AC, Barnett BR, Cohen VJ, Hearn TN, Jones EA, et al. Prenatal nicotine exposure impairs executive control signals in medial prefrontal cortex. Neuropsychopharmacology. 2016; 41(3):716-25.
16. Felson DT, Zhang Y. Smoking and osteoarthritis: a review of the evidence and its implications. Osteoarthritis Cartilage 2015; 23:331-333.
17. Ozdemir ZN, Tazegul G, Kuru P, Bilgin S, Mentese ST, Erzik C, et al. Nicotine alleviates colitis-induced damage in rats via its anti-oxidative activity. Marmara Medical Journal 2014; 27: 13-20
18. Deniz M, Sahin HH, Tekin S, Yeşiller M, Ağaoğlu B, Cetinel S, Yeğen BÇ. Nicotine withdrawal alleviates acetic acid-induced gastric injury in rats.Nicotine withdrawal alleviates acetic acid-induced gastric injury in rats. Environ Toxicol Pharmacol. 2009; 27(2):200-5.
19. Hastrup SG, Chen X, Bechtold JE, Kyle RF, Rahbek O, Keyler DE, et al. Effect of nicotine and tobacco administration method on the mechanical properties of healing bone following closed fracture. J Orthop Res. 2010; 28(9):1235-9.
20. Lee MY, Chen L, Toborek M. Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury. J Neurosci Res 2009; 87:937-947
21. Özdemir-Kumral ZN, Özbeyli D, Özdemir AF, Karaaslan BM, Kaytaz K, Kara MF, et al. Protective effect of nicotine on sepsis-induced oxidative multiorgan damage: role of neutrophils.Nicotine Tob Res. 2017; 19(7):859-864.
22. Hall JE. Guyton & Hall. Textbook of Medical Physiology, 12 th ed., 2011; 60. Bölüm, Çev: Abdullah Arslan, Nobel Tıp Kitabevleri. s. 740.
23. Chowdhury P, Udupa KB. Effect of nicotine on exocytotic pancreatic secretory response: role of calcium signaling. Tob Induc Dis. 2013;11(1):1.
24. Edderkaoui, Mouad. Thrower, Edwin. (2015). Smoking induced pancreatitis and pancreatic cancer. Pancreapedia: Exocrine Pancreas Knowledge Base, DOI: 10.3998/panc.2015.25
25. van Westerloo DJ, Giebelen IA, Florquin S, Bruno MJ, Larosa GJ, Ulloa L, Tracey KJ, et al. The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice. Gastroenterology. 2006; 130(6):1822-30.
26. Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature. 2003; 421(6921):384-8.
27. Ma P, Yu K, Yu J, Wang W, Ding Y, Chen C, et al. Effects of nicotine and vagus nerve in severe acute pancreatitis-associated lung injury in rats. Pancreas. 2016; 45(4):552-60.
28. Holzer HH, Raybould HE. Vagal and splanchnic sensory pathways mediate inhibition of gastric motility induced by duodenal distention. Am J Physiol 1992; 262:G603–G608.
29. Mazelin L, Theodorou V, More J, Fioramonti J, Bueno L. Protective role of vagal afferents in experimentally-induced colitis in rats.J Auton Nerv Syst 1998;73:38–45.
30. Tatewaki M, Harris M, Uemura K, Ueno T, Hoshino E, Shiotani A, et al. Dual effects of acupuncture on gastric motility in conscious rats. Am J Physiol Regul Integr Comp Physiol. 2003; 285(4):R862-72.
31. Schmidt J, Rattner DW, Lewandrowski K, Compton CC, Mandavilli U, Knoefel WT, Warshaw AL: A better model of acute pancreatitis for evaluating therapy. Ann Surg 1992; 215:44-56
32. Sener G, Toklu H, Kapucu C, Ercan F, Erkanli G, Kaçmaz A, Tilki M, Yeğen BC. Melatonin protects against oxidative organ injury in a rat model of sepsis. Surg Today. 2005; 35(1):52-9.
33. Casini A, Ferrali M, Pompella AS, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene intoxicated mice. Am J Pathol. 1986; 123: 520-531
34. Aykac G, Uysal M, Yalcin AS, Kocak-Toker N, Sivas A, Oz H. The effect of chronic ethanol ingestion on hepatic lipidperoxide, glutathione peroxidase and glutathione transferase in rat. Toxicology. 1985; 46: 71-76.
35. Bradley PP, Preibat D, Christerser RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982; 78: 206-209.
36. Di Giovangiulio M, Verheijden S, Bosmans G, Stakenborg N, Boeckxstaens GE, Matteoli G. The neuromodulation of the intestinal immune system and its relevance in inflammatory bowel disease. Front Immunol 2015; 6:59.
37. Van Der Zanden EP, Boeckxstaens GE, de Jonge WJ. The vagus nerve as a modulator of intestinal inflammation. Neurogastroenterol Motil. 2009;21(1):6-17.
38. Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 2004; 10(11):1216-21.
39. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000; 405(6785):458-62.
40. Bernik TR, Friedman SG, Ochani M, DiRaimo R, Ulloa L, Yang H, et al. Pharmacological stimulation of the cholinergic antiinflammatory pathway. J Exp Med 2002; 195(6):781-8.
41. Mioni C, Bazzani C, Giuliani D, Altavilla D, Leone S, Ferrari A, et al. Activation of an efferent cholinergic pathway produces strong protection against myocardial ischemia/reperfusion injury in rats. Crit Care Med. 2005; 33(11):2621-8.
42. Altavilla D, Guarini S, Bitto A, Mioni C, Giuliani D, Bigiani A, et al. Activation of the cholinergic anti-inflammatory pathway reduces NF-kappaB activation, blunts TNF-alpha production, and protects againts splanchic artery occlusion shock. Shock. 2006; 25(5):500-6.
43. Guarini S, Altavilla D, Cainazzo MM, Giuliani D, Bigiani A, Marini H, et al. Efferent vagal fibre stimulation blunts nuclear factor-kappaB activation and protects against hypovolemic hemorrhagic shock. Circulation. 2003; 107(8):1189-94.
44. de Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ, et al. Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol. 2005; 6(8):844-51.
45. L.V. Borovikova, S. Ivanova, D. Nardi, M. Zhang, H. Yang, M. Ombrellino, K.J. Tracey, Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation, Auton. Neurosci. 85 (2000) 141–147].
46. Kolgazi M, Uslu U, Yuksel M, Velioglu-Ogunc A, Ercan F, Alican I. The role of cholinergic anti-inflammatorypathway in acetic acid-induced colonic inflammation in the rat. Chem Biol Interact. 2013; 205 (1): 72–80.
47. Singh P, Garg PK. Pathophysiological mechanisms in acute pancreatitis: Current understanding. Indian J Gastroenterol. 2016 May;35(3):153-66.
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Details

Primary Language	Turkish
Subjects	Internal Diseases
Journal Section	Research Articles
Authors	Meltem Kolgazi Zozan Güleken Bircan Kolbaşı Canberk Sami Başıbüyük Feriha Ercan Berrak Yeğen
Publication Date	April 1, 2021
Submission Date	February 11, 2020
Published in Issue	Year 2021

Cite

EndNote	Kolgazi M, Güleken Z, Kolbaşı B, Başıbüyük CS, Ercan F, Yeğen B (April 1, 2021) Nikotinin Sıçan Pankreatit Modelindeki Hafifletici Etkisinde Vagusun Rolünün Araştırılması. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 12 2 166–175.

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