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Deneysel Kronik Pankreatitte N-Asetil Sistein Uygulamasinin Pankreatik Fibroz Üzerine Etkisi

Yıl 2019, Cilt: 6 Sayı: 1, 26 - 32, 20.03.2019

Öz

Bu çalışmada,
N-asetilsisteinin, kronik pankreatit hayvan modelinde fibrozis, atrofi ve
oksidatif stres üzerindeki etkisini değerlendirmeyi amaçladık. Kronik
pankreatit, ratların ana pankreatik kanallarına 0.4 ml, %2’lik trinitrobenzen
sülfanik asit (TNBS) enjeksiyonu ile uyarılır. 60 Sprague-Dawley sıçanı dört
gruba randomize edildi; Grup I (n= 15): salin (sham), Grup II (n= 15): fibrozis
+ N-asetilsistein (NAC), Grup III (n= 15): fibrozis (TNBS), Grup IV: etanol. 8.
haftanın sonunda tüm ratlar sakrefiye edildi ve pankreatik dokular, oksidatif
stres belirteçleri, fibrozis ve atrofi progresyonları incelendi. NAC grubunda
doku malondialdehid (MDA) düzeyleri anlamlı olarak düşük bulunurken (p <0.001);
süperoksit dismutaz (SOD) ve glutation peroksidaz (GSH-Px) aktiviteleri TNBS
grubuna göre anlamlı olarak yüksek bulundu (sırasıyla p <0.001 ve p <0.001).
Dokulardaki histopatolojik incelemede NAC grubunun histopatolojik skorunun TNBS
grubundan anlamlı derecede düşük olduğu izlenirken (p<0.003) oksidatif stres
ile histopatolojik skordaki artış arasında anlamlı bir ilişki olduğu saptandı
(histopatolojik skor/MDA: p<0.03, SOD: p<0.04, GSH-Px: p<0.02). Sonuç
olarak, NAC uygulaması kronik pankreatitte oksidatif stresi azaltmakta olup
fibrozis ve atrofi üzerinde yararlı etkilere sahiptir.

Kaynakça

  • 1. Gupte AR, Forsmark CE. Chronic pancreatitis. Curr Opin Gastroenterol. 2014;30(5):500-5.
  • 2. Patel M, Fine DR. Fibrogenesis in the pancreas after acinar cell injury. Scand J Surg. 2005;94(2):108-11.
  • 3. Goh KL. Chronic pancreatitis: aetiology, epidemiology and clinical presentation. Med J Malaysia. 2005;60(Suppl B):94-8.
  • 4. Dryden GW Jr, Deaciuc I, Arteel G, McClain CJ. Clinical implications of oxidative stress and antioxidant therapy. Curr Gastroenterol Rep. 2005;7(4):308-16.
  • 5. Kakizaki S, Hamada T, Yoshinaga T, et al. Alcoholic chronic pancreatitis with simultaneous multiple severe complications-extrahepatic portal obliteration, obstructive jaundice and duodenal stricture. Hepatogastroenterology. 2005;52(64):1274-7.
  • 6. Gullo L, Migliori M, Brunetti MA, Manca M. Alcoholic pancreatitis: new insights into an old disease. Curr Gastroenterol Rep. 2005;7(2):96-100.
  • 7. Apte MV, Wilson JS. Mechanisms of pancreatic fibrosis. Dig Dis. 2004;22(3):273-9.
  • 8. Connelly E. Chronic pancreatitis debilitating for the patient, frustrating to manage. JAAPA. 2004;17(12):14-6.
  • 9. Bruno MJ. Chronic pancreatitis. Gastrointest Endosc Clin N Am. 2005;15(1):55-62.
  • 10. Schneider A, Whitcomb DC, Singer MV. Animal models in alcoholic pancreatitis-what can we learn? Pancreatology. 2002;2(3):189-203.
  • 11. Azima B, Kao RL, Youngberg G, Williams D, Browder W. A new animal model of reversible acute pancreatitis. J Surg Res. 1996;63(2):419-24.
  • 12. Zhou D, Wang W, Cheng X, Wei J, Zheng S. Antioxidant therapy for patients with chronic pancreatitis: A systematic review and meta-analysis. Clin Nutr. 2015;34(4):627-34.
  • 13. Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med. 1989;6(6):593-7.
  • 14. De Vries N, De Flora S. N-Acetyl-l-Cysteine. J Cell Biochem. 1993;17F:S270-7.
  • 15. Sevillano S, De la Mano AM, De Dios I, Ramudo L, Manso MA. Major pathological mechanisms of acute pancreatitis are prevented by N-acetylcysteine. Digestion. 2003;68(1):34-40.
  • 16. Yağcı G, Gül H, Simsek A, et al. Beneficial effects of N-acetylcysteine on sodium taurocholate-induced pancreatitis in rats. J Gastroenterol. 2004;39(3):268-76.
  • 17. Choudhury S, Ghosh S, Gupta P, Mukherjee S, Chattopadhyay S. Inflammation-induced ROS generation causes pancreatic cell death through modulation of Nrf2/NF-κB and SAPK/JNK pathway. Free Radic Res. 2015;49(11):1371-83.
  • 18. Haber PS, Keogh GW, Apte MV. Pancreatic stellate cells are activated in human and experimental pancreatitis. Gut. 1999;44:534-41.
  • 19. Puig-Divi V, Molero X, Slas A. Induction of chronic pancreatic disease by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts. Pancreas. 1996;13(4):417-24.
  • 20. Aydın A, Orhan H, Sayal A, Ozata M, Sahin G, Işimer A. Oxidative stress and nitric oxide related parameters in type ıı diabetes mellitus: effects of glycemic control. Clin Biochem. 2001;34(1):65-70.
  • 21. Richard MJ, Arnaud J, Jurkowitz C, et al. Trace elements and lipid peroxidation abnormalities ın patients with chronic renal failure. Nephron. 1991;57(1):10-5.
  • 22. Braganza JM, Scott P. Bilton D. Evidence for early oxidative stress in acute pancreatitis. Int J Pancreatol. 1995;17(1):69-81.
  • 23. Mathew P, Wyllie R, VanLente F, Steffen RM, Kay MH. Antioxidants In Hereditary Pancreatitis. Am J Gastroenterol. 1996;91(8):1558-62.
  • 24. Morris-Stiff GJ, Bowrey DJ, Oleesky D. The antioxidant profiles of patients with recurrent acute and chronic pancreatitis. Am J Gastroenterol. 1999;94(8):2136-40.
  • 25. Van Gossum A, Closset P, Noel E, Cremer M, Neve J. Deficiency in antioxidant factors in patients with alcohol-related chronic pancreatitis. Dig Dis Sci. 1996;41(6):1225-31.
  • 26. Matsumura N, Ochi K, Ichimura M, Mizushima T, Harada H, Harada M. Study on free radicals and pancreatic fibrosis–pancreatic fibrosis induced by repeated injections of superoxyde dismutase inhibitor. Pancreas. 2001;22(1):53-7.
  • 27. Rose P, Fraine E, Hunt LP, Acheson DW, Braganza JM. Dietary antioxidants and chronic pancreatitis. Hum Nutr Clin Nutr. 1986;40(2):151-64.
  • 28. Castano H, Unzueta G, Agustín Domínguez D, et al. Pancreatic fibrosis in rats and ıts response to antioxidant treatment. JOP. 2005;6(4):316-24.
  • 29. Mas R, Işık AT, Yamanel L, et al. Antioxidant treatment with taurine ameliorates chronic pancreatitis in an experimental rat model. Pancreas. 2006;33(1):77-81.
  • 30. Ozturk K, Tasci I, Yasar M, et al. Effects of rapamycin treatment on pancreatic fibrosis, cellular apoptosis and oxidative stress in experimental chronic pancreatitis model. Acta Gastroenterol Belg. 2015;78(1):3-7.
  • 31. Sapronov NS, Khnychenko LK, Polevschikov AV. Effects of taurine derivatives on primaryy ımmune response. Bull Exp Biol Med. 2001;131(2):142-4.
  • 32. Denham W, Fink G, Yang J, Ulrich P, Tracey K, Norman J. Small molecule ınhibition of tnf gene processing during acute pancreatitis prevents cytokine cascade progression and attenuates pancreatitis severity. Am Surg. 1997;63(12):1045-9.
  • 33. Ethride RT, Hashimoto K, Chung DH, Ehlers RA, Rajaraman S, Evers BM. Selective inhibition of NF-kappa B attenuates the severity of cerulein-induced acute pancreatitis. J Am Coll Surg. 2002;195(4):497-505.
  • 34. Hughes CB, Grewal HP, Gaber LW, et al. Anti-TNFα therapy ımproves survival and ameliorates the pathophysiological sequale in acute pancreatitis in the rat. Am J Surg. 1996;171(2); 274-80.
  • 35. Ahn BO, Kim HG, Lee HS, et al. Effects of taurine on cerulein-induced acute pancreatitis in the rat. Pharmacology. 2001;63(1):1-7.
  • 36. Gomez JA, Molero X, VaqueroE, Alonso A, Salas A, Malagelada JR. Vitamin E attenuates biochemical and morphological features associated with development of chronic pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2004;287:162-9.
  • 37. Seo JY, Kim H, Seo JT, Kim KH. Oxidative stress induced cytokine production in isolated rat pancreatic aciner cells: effects of small-molecule antioxidants, Pharmacology. 2002;64(2):63-70.
  • 38. Kim H, Seo JY, Roh KH, Lim JW, Kim KH. Suppression of NF-κB activation and cytokine production by N-Acetylcystein in pancreatic aciner cells. Free Radic Biol Med. 2000;29(7):674-83.
  • 39. Okazaki I, Watanabe T, Hozawa S, Arai M, Maruyama K. Molecular mechanism of the reversibility of matrix metalloproteinase’s. Hepatology. 2000;15(1):26-32.
  • 40. De Caro L, Ghizzi A, Costa R, Longo A, Ventresca GP, Lodola E. Pharmacokinetics and bioavailability of oral acetylcysteine in healthy volunteers. Arzneim Forsch. 1989;39(3):382-5.
  • 41. Olsson B, Johansson M, Gabrielsson J, Bolme P. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol. 1988;34(1):77-82.
  • 42. Wagner PD, Mathieu-Costello O, Bebout DE, et al. Protection against pulmonary O2 toxicity by N-acetylcysteine. Protection against pulmonary O2 toxicity by N-acetylcysteine. Eur Respir J. 1989;2(2):116-26.
  • 43. Demols A, Van Laethem JL, Quertinmont E, et al. N-acetylcysteine decreases severity of acute pancreatitis in mice. Pancreas. 2000;20(2):161-9.
  • 44. Kim H, Seo JY, Kim KH. NF-kappaB and cytokines in pancreatic acinar cells. J Korean Med Sci. 2000;15:53-4.
  • 45. Bhatia M, Brady M, Kang YK, et al. MCP-1 but not CINC synthesis is increased in rat pancreatic acini in response to cerulein hyperstimulation. Am J Physiol Gastrointest Liver Physiol. 2002;282(1):77-85.
  • 46. Haraldsen P, Sun ZW, Börjesson A, Olanders K, Lasson A, Andersson R. Multimodal management of value in fulminant acute pancreatitis? Pancreatology. 2003;3(1):14-25.
  • 47. Shi C, Zhao X, Wang X, Andersson R. Role of nuclear factor-kappaB, reactive oxygen species and cellular signaling in the early phase of acute pancreatitis. Scand J Gastroenterol. 2005;40(1):103-8.
  • 48. Eşrefoğlu M, Gül M, Ateş B, Yilmaz I. Ultrastructural clues for the protective effect of ascorbic acid and N-acetylcysteine against oxidative damage on caerulein-induced pancreatitis. Pancreatology. 2006;6(5):477-85.
  • 49. Kalyoncu NI, Alhan E, Ercin C, Kural BV. Effects of dual inhibitor of cyclooxygenase and 5-lipoxygenase on acute necrotizing pancreatitis in rats. Hepatogastroenterology. 2006;53(70):597-602.
  • 50. Sevillano S, de Dios I, de la Mano AM, Manso MA. N-acetylcysteine induces beneficial changes in the acinar cell cycle progression in the course of acute pancreatitis. Cell Prolif. 2003;36(5):279-89.
  • 51. Sevillano S, de la Mano AM, Manso MA. N-acetylcysteine prevents intra-acinar oxygen free radical production in pancreatic duct obstruction-induced acute pancreatitis. Biochim Biophys Acta. 2003;36(5):279-89.
  • 52. Asaumi H, Watanabe S, Taguchi M, Tashiro M, Otsuki M. Externally-applied pressure activates pancreatic stellate cells through the generation of intracellular reactive oxygen species, Am J Physiol Gastrointest Liver Physiol. 2007;293(5):972-8.
  • 53. Menke A, Adler G. TGF Beta-induced fibrogenesis of the pancreas. Int J Gastrointest Cancer. 2002;31(1-3):41-6.
  • 54. Shek FWT, Benyon RC, Walker FM, et al. Expression of transforming growth factor-β1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis. Am J Pathol. 2002;160(5):1787-98.

The Effect of N-Acetylcysteine on Fibrosis in Experimental Rat Chronic Pancreatitis

Yıl 2019, Cilt: 6 Sayı: 1, 26 - 32, 20.03.2019

Öz










In this study, we
aimed to assess the effect of N-acetylcysteine on fibrosis, atrophy and
oxidative stress with chronic pancreatitis in an animal model. Chronic
pancreatitis is stimulated by injection of 0.4 ml, 2% trinitrobenzene sulfanic
acid (TNBS) into major pancreatic ducts of the rats. 60 Sprague-Dawley rats
were randomized into four group; Group I (n=15): saline (control), Grup II
(n=15): fibrosis + N-acetylcysteine (NAC), Grup III (n=15): fibrosis (TNBS),
Grup IV: ethanol. At the end of the 8th week, all rats were sacrificed, and rat
pancreatic tissues, oxidative stress markers and progression of fibrosis and
atrophy were examined. superoxide dismutase (SOD) and glutation peroxidase
(GSH-Px) activities were significantly higher with respect to TNBS group
(respectively p<0.001 and p<0.001); whereas tissue malondialdehyde (MDA)
levels were found significantly lower in NAC group (p<0.001). 
Histopathological analysis of the tissues
revealed that histopathological score of NAC group was significantly lower than
TNBS group (p<0.003), and was found a significant relation between increase
in oxidative stress and histopathological score (histopathological score/MDA:
p<0.03, SOD: p<0.04, GSH-Px: p<0,02). In conclusion, administration of
NAC decreases oxidative stress in chronic pancreatitis and has beneficial
effects on fibrosis and atrophy.

Kaynakça

  • 1. Gupte AR, Forsmark CE. Chronic pancreatitis. Curr Opin Gastroenterol. 2014;30(5):500-5.
  • 2. Patel M, Fine DR. Fibrogenesis in the pancreas after acinar cell injury. Scand J Surg. 2005;94(2):108-11.
  • 3. Goh KL. Chronic pancreatitis: aetiology, epidemiology and clinical presentation. Med J Malaysia. 2005;60(Suppl B):94-8.
  • 4. Dryden GW Jr, Deaciuc I, Arteel G, McClain CJ. Clinical implications of oxidative stress and antioxidant therapy. Curr Gastroenterol Rep. 2005;7(4):308-16.
  • 5. Kakizaki S, Hamada T, Yoshinaga T, et al. Alcoholic chronic pancreatitis with simultaneous multiple severe complications-extrahepatic portal obliteration, obstructive jaundice and duodenal stricture. Hepatogastroenterology. 2005;52(64):1274-7.
  • 6. Gullo L, Migliori M, Brunetti MA, Manca M. Alcoholic pancreatitis: new insights into an old disease. Curr Gastroenterol Rep. 2005;7(2):96-100.
  • 7. Apte MV, Wilson JS. Mechanisms of pancreatic fibrosis. Dig Dis. 2004;22(3):273-9.
  • 8. Connelly E. Chronic pancreatitis debilitating for the patient, frustrating to manage. JAAPA. 2004;17(12):14-6.
  • 9. Bruno MJ. Chronic pancreatitis. Gastrointest Endosc Clin N Am. 2005;15(1):55-62.
  • 10. Schneider A, Whitcomb DC, Singer MV. Animal models in alcoholic pancreatitis-what can we learn? Pancreatology. 2002;2(3):189-203.
  • 11. Azima B, Kao RL, Youngberg G, Williams D, Browder W. A new animal model of reversible acute pancreatitis. J Surg Res. 1996;63(2):419-24.
  • 12. Zhou D, Wang W, Cheng X, Wei J, Zheng S. Antioxidant therapy for patients with chronic pancreatitis: A systematic review and meta-analysis. Clin Nutr. 2015;34(4):627-34.
  • 13. Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med. 1989;6(6):593-7.
  • 14. De Vries N, De Flora S. N-Acetyl-l-Cysteine. J Cell Biochem. 1993;17F:S270-7.
  • 15. Sevillano S, De la Mano AM, De Dios I, Ramudo L, Manso MA. Major pathological mechanisms of acute pancreatitis are prevented by N-acetylcysteine. Digestion. 2003;68(1):34-40.
  • 16. Yağcı G, Gül H, Simsek A, et al. Beneficial effects of N-acetylcysteine on sodium taurocholate-induced pancreatitis in rats. J Gastroenterol. 2004;39(3):268-76.
  • 17. Choudhury S, Ghosh S, Gupta P, Mukherjee S, Chattopadhyay S. Inflammation-induced ROS generation causes pancreatic cell death through modulation of Nrf2/NF-κB and SAPK/JNK pathway. Free Radic Res. 2015;49(11):1371-83.
  • 18. Haber PS, Keogh GW, Apte MV. Pancreatic stellate cells are activated in human and experimental pancreatitis. Gut. 1999;44:534-41.
  • 19. Puig-Divi V, Molero X, Slas A. Induction of chronic pancreatic disease by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts. Pancreas. 1996;13(4):417-24.
  • 20. Aydın A, Orhan H, Sayal A, Ozata M, Sahin G, Işimer A. Oxidative stress and nitric oxide related parameters in type ıı diabetes mellitus: effects of glycemic control. Clin Biochem. 2001;34(1):65-70.
  • 21. Richard MJ, Arnaud J, Jurkowitz C, et al. Trace elements and lipid peroxidation abnormalities ın patients with chronic renal failure. Nephron. 1991;57(1):10-5.
  • 22. Braganza JM, Scott P. Bilton D. Evidence for early oxidative stress in acute pancreatitis. Int J Pancreatol. 1995;17(1):69-81.
  • 23. Mathew P, Wyllie R, VanLente F, Steffen RM, Kay MH. Antioxidants In Hereditary Pancreatitis. Am J Gastroenterol. 1996;91(8):1558-62.
  • 24. Morris-Stiff GJ, Bowrey DJ, Oleesky D. The antioxidant profiles of patients with recurrent acute and chronic pancreatitis. Am J Gastroenterol. 1999;94(8):2136-40.
  • 25. Van Gossum A, Closset P, Noel E, Cremer M, Neve J. Deficiency in antioxidant factors in patients with alcohol-related chronic pancreatitis. Dig Dis Sci. 1996;41(6):1225-31.
  • 26. Matsumura N, Ochi K, Ichimura M, Mizushima T, Harada H, Harada M. Study on free radicals and pancreatic fibrosis–pancreatic fibrosis induced by repeated injections of superoxyde dismutase inhibitor. Pancreas. 2001;22(1):53-7.
  • 27. Rose P, Fraine E, Hunt LP, Acheson DW, Braganza JM. Dietary antioxidants and chronic pancreatitis. Hum Nutr Clin Nutr. 1986;40(2):151-64.
  • 28. Castano H, Unzueta G, Agustín Domínguez D, et al. Pancreatic fibrosis in rats and ıts response to antioxidant treatment. JOP. 2005;6(4):316-24.
  • 29. Mas R, Işık AT, Yamanel L, et al. Antioxidant treatment with taurine ameliorates chronic pancreatitis in an experimental rat model. Pancreas. 2006;33(1):77-81.
  • 30. Ozturk K, Tasci I, Yasar M, et al. Effects of rapamycin treatment on pancreatic fibrosis, cellular apoptosis and oxidative stress in experimental chronic pancreatitis model. Acta Gastroenterol Belg. 2015;78(1):3-7.
  • 31. Sapronov NS, Khnychenko LK, Polevschikov AV. Effects of taurine derivatives on primaryy ımmune response. Bull Exp Biol Med. 2001;131(2):142-4.
  • 32. Denham W, Fink G, Yang J, Ulrich P, Tracey K, Norman J. Small molecule ınhibition of tnf gene processing during acute pancreatitis prevents cytokine cascade progression and attenuates pancreatitis severity. Am Surg. 1997;63(12):1045-9.
  • 33. Ethride RT, Hashimoto K, Chung DH, Ehlers RA, Rajaraman S, Evers BM. Selective inhibition of NF-kappa B attenuates the severity of cerulein-induced acute pancreatitis. J Am Coll Surg. 2002;195(4):497-505.
  • 34. Hughes CB, Grewal HP, Gaber LW, et al. Anti-TNFα therapy ımproves survival and ameliorates the pathophysiological sequale in acute pancreatitis in the rat. Am J Surg. 1996;171(2); 274-80.
  • 35. Ahn BO, Kim HG, Lee HS, et al. Effects of taurine on cerulein-induced acute pancreatitis in the rat. Pharmacology. 2001;63(1):1-7.
  • 36. Gomez JA, Molero X, VaqueroE, Alonso A, Salas A, Malagelada JR. Vitamin E attenuates biochemical and morphological features associated with development of chronic pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2004;287:162-9.
  • 37. Seo JY, Kim H, Seo JT, Kim KH. Oxidative stress induced cytokine production in isolated rat pancreatic aciner cells: effects of small-molecule antioxidants, Pharmacology. 2002;64(2):63-70.
  • 38. Kim H, Seo JY, Roh KH, Lim JW, Kim KH. Suppression of NF-κB activation and cytokine production by N-Acetylcystein in pancreatic aciner cells. Free Radic Biol Med. 2000;29(7):674-83.
  • 39. Okazaki I, Watanabe T, Hozawa S, Arai M, Maruyama K. Molecular mechanism of the reversibility of matrix metalloproteinase’s. Hepatology. 2000;15(1):26-32.
  • 40. De Caro L, Ghizzi A, Costa R, Longo A, Ventresca GP, Lodola E. Pharmacokinetics and bioavailability of oral acetylcysteine in healthy volunteers. Arzneim Forsch. 1989;39(3):382-5.
  • 41. Olsson B, Johansson M, Gabrielsson J, Bolme P. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol. 1988;34(1):77-82.
  • 42. Wagner PD, Mathieu-Costello O, Bebout DE, et al. Protection against pulmonary O2 toxicity by N-acetylcysteine. Protection against pulmonary O2 toxicity by N-acetylcysteine. Eur Respir J. 1989;2(2):116-26.
  • 43. Demols A, Van Laethem JL, Quertinmont E, et al. N-acetylcysteine decreases severity of acute pancreatitis in mice. Pancreas. 2000;20(2):161-9.
  • 44. Kim H, Seo JY, Kim KH. NF-kappaB and cytokines in pancreatic acinar cells. J Korean Med Sci. 2000;15:53-4.
  • 45. Bhatia M, Brady M, Kang YK, et al. MCP-1 but not CINC synthesis is increased in rat pancreatic acini in response to cerulein hyperstimulation. Am J Physiol Gastrointest Liver Physiol. 2002;282(1):77-85.
  • 46. Haraldsen P, Sun ZW, Börjesson A, Olanders K, Lasson A, Andersson R. Multimodal management of value in fulminant acute pancreatitis? Pancreatology. 2003;3(1):14-25.
  • 47. Shi C, Zhao X, Wang X, Andersson R. Role of nuclear factor-kappaB, reactive oxygen species and cellular signaling in the early phase of acute pancreatitis. Scand J Gastroenterol. 2005;40(1):103-8.
  • 48. Eşrefoğlu M, Gül M, Ateş B, Yilmaz I. Ultrastructural clues for the protective effect of ascorbic acid and N-acetylcysteine against oxidative damage on caerulein-induced pancreatitis. Pancreatology. 2006;6(5):477-85.
  • 49. Kalyoncu NI, Alhan E, Ercin C, Kural BV. Effects of dual inhibitor of cyclooxygenase and 5-lipoxygenase on acute necrotizing pancreatitis in rats. Hepatogastroenterology. 2006;53(70):597-602.
  • 50. Sevillano S, de Dios I, de la Mano AM, Manso MA. N-acetylcysteine induces beneficial changes in the acinar cell cycle progression in the course of acute pancreatitis. Cell Prolif. 2003;36(5):279-89.
  • 51. Sevillano S, de la Mano AM, Manso MA. N-acetylcysteine prevents intra-acinar oxygen free radical production in pancreatic duct obstruction-induced acute pancreatitis. Biochim Biophys Acta. 2003;36(5):279-89.
  • 52. Asaumi H, Watanabe S, Taguchi M, Tashiro M, Otsuki M. Externally-applied pressure activates pancreatic stellate cells through the generation of intracellular reactive oxygen species, Am J Physiol Gastrointest Liver Physiol. 2007;293(5):972-8.
  • 53. Menke A, Adler G. TGF Beta-induced fibrogenesis of the pancreas. Int J Gastrointest Cancer. 2002;31(1-3):41-6.
  • 54. Shek FWT, Benyon RC, Walker FM, et al. Expression of transforming growth factor-β1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis. Am J Pathol. 2002;160(5):1787-98.
Toplam 54 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İç Hastalıkları
Bölüm Araştırma Makalesi
Yazarlar

Ramazan Ocal 0000-0002-9087-4806

İlker Tascı Bu kişi benim 0000-0002-0936-2476

Mehmet Salih Devecı Bu kişi benim 0000-0001-6234-3488

Bilgin Comert Bu kişi benim 0000-0002-2148-5356

Ahmet Turan Isık Bu kişi benim 0000-0001-5867-6503

Mehmet Refik Mas Bu kişi benim 0000-0003-4874-9603

Yayımlanma Tarihi 20 Mart 2019
Gönderilme Tarihi 7 Aralık 2018
Yayımlandığı Sayı Yıl 2019 Cilt: 6 Sayı: 1

Kaynak Göster

APA Ocal, R., Tascı, İ., Devecı, M. S., Comert, B., vd. (2019). The Effect of N-Acetylcysteine on Fibrosis in Experimental Rat Chronic Pancreatitis. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, 6(1), 26-32.
AMA Ocal R, Tascı İ, Devecı MS, Comert B, Isık AT, Mas MR. The Effect of N-Acetylcysteine on Fibrosis in Experimental Rat Chronic Pancreatitis. MMJ. Mart 2019;6(1):26-32.
Chicago Ocal, Ramazan, İlker Tascı, Mehmet Salih Devecı, Bilgin Comert, Ahmet Turan Isık, ve Mehmet Refik Mas. “The Effect of N-Acetylcysteine on Fibrosis in Experimental Rat Chronic Pancreatitis”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 6, sy. 1 (Mart 2019): 26-32.
EndNote Ocal R, Tascı İ, Devecı MS, Comert B, Isık AT, Mas MR (01 Mart 2019) The Effect of N-Acetylcysteine on Fibrosis in Experimental Rat Chronic Pancreatitis. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 6 1 26–32.
IEEE R. Ocal, İ. Tascı, M. S. Devecı, B. Comert, A. T. Isık, ve M. R. Mas, “The Effect of N-Acetylcysteine on Fibrosis in Experimental Rat Chronic Pancreatitis”, MMJ, c. 6, sy. 1, ss. 26–32, 2019.
ISNAD Ocal, Ramazan vd. “The Effect of N-Acetylcysteine on Fibrosis in Experimental Rat Chronic Pancreatitis”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 6/1 (Mart 2019), 26-32.
JAMA Ocal R, Tascı İ, Devecı MS, Comert B, Isık AT, Mas MR. The Effect of N-Acetylcysteine on Fibrosis in Experimental Rat Chronic Pancreatitis. MMJ. 2019;6:26–32.
MLA Ocal, Ramazan vd. “The Effect of N-Acetylcysteine on Fibrosis in Experimental Rat Chronic Pancreatitis”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, c. 6, sy. 1, 2019, ss. 26-32.
Vancouver Ocal R, Tascı İ, Devecı MS, Comert B, Isık AT, Mas MR. The Effect of N-Acetylcysteine on Fibrosis in Experimental Rat Chronic Pancreatitis. MMJ. 2019;6(1):26-32.