Ultrastructural aspects of acute pancreatitis induced by 2, 2’-azobis (2-amidinopropane) dihydrochloride (AAPH) in rats

• Autorzy: Tukaj C. , Olewniak-Adamowska A. , Pirski M. I. , Wozniak M.
• Języki publikacji: EN

Abstrakty

EN

Pathophysiology of acute pancreatitis (AP) has not been clearly established; nevertheless, accumulating evidence implicates highly reactive oxygen species (ROS) as important mediators of exocrine tissue damage. In this study, we used a water-soluble radical initiator, 2,2’-azobis-(2-amidinopropane) dihydrochloride (AAPH), to investigate the consequences of oxidative stress insult to the rat pancreas. The detailed characterisation of acini ultrastructural changes in the early course (3, 6, 12, 24 h) of AAPH-induced pancreatitis (40 mg/1 kg body weight) was performed. Considerable damage to the mitochondria in acinar cells manifested by increased translucence of the matrix, partial destruction of cristae, and formation of myelin figures were noted. At the same time, focal dilation, degranulation of rough endoplasmic reticulum, and reduced number of zymogen granules was observed. The most prominent ultrastructural feature was accumulation of highly polymorphic cytoplasmic vacuoles in acinar cells. Double membrane-bound autophagosomes, different in size and shape, with sequestered organelles, autophagolysosomes, and large, empty, single-membrane-bound vacuoles were observed within the cytoplasm. The results indicate that intensive and impaired autophagy mediates pathological accumulation of vacuoles in acinar cells. The rat model of acute pancreatitis induced by AAPH is useful to investigate the early events of oxidative stress insult to the pancreas. (Folia Morphol 2012; 71, 3: 136–141)

• Wydawca: -
• Czasopismo: Folia Morphologica
• Rocznik: 2012
• Tom: 71
• Numer: 3
• Opis fizyczny: p.136-141,fig.,ref.

Twórcy

autor

Tukaj C.

• Department of Electron Microscopy, Medical University of Gdansk, ul.Debinki 1, 80–210 Gdansk, Poland

autor

Olewniak-Adamowska A.

• Department of Electron Microscopy, Medical University of Gdansk, ul.Debinki 1, 80–210 Gdansk, Poland

autor

Pirski M. I.

• Powislanski College in Kwidzyn, Poland

autor

Wozniak M.

• Department of Medical Chemistry, Medical University of Gdansk, Poland

Bibliografia

• 1. Andrzejewska A, Jurkowska G (1999) Nitric oxide protects the ultrastructure of pancreatic acinar cells in the course of caerulein-induced acute pancreatitis. Int J Exp Pathol, 80: 317–724.
• 2. Bockman DE (1997) Morphology of the exocrine pancreas related to pancreatitis. Microsc Res Tech, 37: 509–519.
• 3. Cecconi F, Beth L (2008) The role of autophagy in mammalian development cell makeover rather than cell death. Dev Cell, 15: 344–357.
• 4. Dunn WA Jr. (1990) Studies on the mechanisms of autophagy: maturation of the autophagic vacuole. J Cell Biol, 110: 1935–1945.
• 5. Fortunato F, Kroemer G (2009) Impaired autophagosome-lysosome fusion in the pathogenesis of pancreatitis. Autophagy, 5: 850–853.
• 6. Green DR, Galluzzi L, Kroemer G (2011) Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science, 26: 1109–1112.
• 7. Gukovskaya AS, Gukovsky I (2011) Which way to die: the regulation of acinar cell death in pancreatitis by mitochondria, calcium, and reactive oxygen species. Gastroenterology, 140: 1876–1880.
• 8. Gukovsky I, Gukovskaya AS (2010) Impaired autophagy underlies key pathological responses of acute pancreatitis. Autophagy, 6: 428–429.
• 9. Gukovsky I, Pandol SJ, Mareninova OA, Shalbueva N, Jia W, Gukovskaya AS (2012) Impaired autophagy and organellar dysfunction in pancreatitis. J Gastroenterol Hepatol, 27 (suppl. 2): 27–32.
• 10. Hashimoto D, Ohmuraya M, Hirota M, Yamamoto A, Suyama K, Ida S, Okumura Y, Takahashi E, Kido H, Araki K, Baba H, Mizushima N, Yamamura K (2008) Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells. Autophagy, 4: 1060–1062.
• 11. Hernandez L, Grasa L, Fagundes DS, Gonzalo S, Arruebo MP, Plaza MA, Murillo MD (2010) Role of potassium channels in rabbit intestinal motility disorders induced by 2, 2’-azobis (2-amidinopropane) dihydrochloride (AAPH). J Physiol Pharmacol, 61: 279–286.
• 12. Kanno T, Utsumi T, Ide A, Takehara Y, Saibara T, Akiyama J, Yoshioka T, Utsumi K (1994) Dysfunction of mouse liver mitochondria induced by 2,2’-azobis-(2-amidinopropane) dihydrochloride, a radical initiator, in vitro and in vivo. Free Radic Res, 21: 223–234.
• 13. Kikuchi Y, Shimosegawa T, Moriizumi S, Kimura K, Satoh A, Koizumi M, Kato I, Epstein CJ, Toyota T (1997) Transgenic copper/zinc superoxide dismutase ameliorates caerulein-induced pancreatitis in mice. Biochem Biophys Res Commun, 233: 1277–1281.
• 14. Kim JN, Lee HS, Ryu SH, Kim YS, Moon JS, Kim CD, Chang IY, Yoon SP (2011) Heat shock proteins and autophagy in rats with cerulein-induced acute pancreatitis. Gut Liver, 5: 513–520.
• 15. Klöppel G, Dreyer T, Willemer S, Kern HF, Adler G (1986) Human acute pancreatitis: its pathogenesis in the light of immunocytochemical and ultrastructural findings in acinar cells. Virchows Arch A Pathol Anat Histopathol, 409: 791–803.
• 16. Lawinski M, Sledzinski Z, Kubasik-Juraniec J, Spodnik JH, Wozniak M, Boguslawski W (2005) Does resveratrol prevent free radical-induced acute pancreatitis? Pancreas, 31: 43–47.
• 17. Long J, Song N, Liu XP, Guo KJ, Guo RX (2005) Nuclear factor-kappaB activation on the reactive oxygen species in acute necrotizing pancreatitic rats. World J Gastroenterol, 21: 4277–4280.
• 18. Niederau C, Grendell JH (1988) Intracellular vacuoles in experimental acute pancreatitis in rats and mice are an acidified compartment. J Clin Invest, 81: 229–236.
• 19. Ohmuraya M, Yamamura K (2008) A novel autophagy theory for trypsinogen activation. Autophagy, 4: 1060–1062.
• 20. Peluso I, Campolongo P, Valeri P, Romanelli L, Palmery M (2002) Intestinal motility disorder induced by free radicals: a new model mimicking oxidative stress in gut. Pharmacol Res, 46: 533–538.
• 21. Petrov MS (2010) Therapeutic implications of oxidative stress in acute and chronic pancreatitis. Curr Opin Clin Nutr Metab Care, 13: 562–568.
• 22. Petrov MS, Windsor JA (2010) Classification of the severity of acute pancreatitis: how many categories make sense? Am J Gastroenterol, 105: 74–76.
• 23. Raraty MG, Connor S, Criddle DN, Sutton R, Neoptolemos P (2004) Acute pancreatitis and organ failure: pathophysiology, natural history, and management strategies. Curr Gastroenterol Rep, 6: 99–103.
• 24. Rau B, Poch B, Gansauge F, Bauer A, Nüssler AK, Nevalainen T, Schoenberg MH, Beger HG (2000) Pathophysiologic role of oxygen free radicals in acute pancreatitis initiating event or mediator of tissue damage? Ann Surg, 231: 352–360.
• 25. Sanfey H, Bulkley GB, Cameron JL (1984) The role of oxygen-derived free radicals in the pathogenesis of acute pancreatitis. Ann Surg, 200: 405–413.
• 26. Schulz HU, Niederau C, Klonowski-Stumpe H, Halangk W, Luthen R, Lippert H (1999) Oxidative stress in acute pancreatitis. Hepatogastroenterology, 46: 2736–2750.
• 27. Sherwood MW, Prior IA, Voronina SG, Barrow SL, Woodsmith JD, Gerasimenko OV, Petersen OH, Tepikin AV (2007) Activation of trypsinogen in large endocytic vacuoles of pancreatic acinar cells. Proc Natl Acad Sci USA, 104: 5674–5679.
• 28. Sweiry JH, Mann GE (1996) Role of oxidative stress in the pathogenesis of acute pancreatitis. Scand J Gastroenterol Suppl, 219: 10–15.
• 29. Watanabe O, Baccino FM, Steer ML, Meldolesi J (1984) Supramaximal caerulein stimulation and ultrastructure of rat pancreatic acinar cell: early morphological changes during development of experimental pancreatitis. Am J Physiol, 246: 457–467.
• 30. Willemer S, Adler G (1991) Mechanism of acute pancreatitis. Cellular and subcellular events. Int J Pancreatol, 9: 21–30.