Peculiarities of death and regeneration of pancreas cells at early stages of alcoholic chronic pancreatitis

  • N. Y. Oshmyanska State Institution "Institute of Gastroenterology of NAMS of Ukraine"
  • A. A. Galinsky State Institution "Institute of Gastroenterology of NAMS of Ukraine"
  • Y. A. Gaidar State Institution "Institute of Gastroenterology of NAMS of Ukraine"
Keywords: chronic pancreatitis, pancreatic islets, PCNA, Neurogenin-3


The study has been conducted on 39 white laboratory male rats which formed 5 groups: experimental occlusal pancreatitis caused by ligation of the main pancreatic duct (n = 6), experimental alcoholic pancreatitis caused by oral intake of alcohol (n = 6), against the background of an excess (n = 6) or deficiency (n = 6) of nitric oxide, as well as a control group (n = 15). This study provides the detailed description of the processes of death and regeneration in the islets of Langerhans, typical for early stages of the disease. The expression of the proliferation markers (PCNA and Neurogenin-3) has been analyzed using histological and immunohistochemical methods along with the changes of morphological structure, that led to initiation of the alcoholic chronic pancreatitis against the background of imbalance in NO-ergic regulatory system caused by an excess or deficiency of nitric oxide. It has been found that ligation of the pancreatic duct in the experiment reconstructedthe circumstances of chronic pancreatitis in rats and caused the activation of fibrosis and regeneration of endocrine and exocrine tissue. Compared with occlusion, the effects of ethanol on the pancreas also manifested in the activation of fibrogenesis, but the structural changes were negligible and could unlikely lead to advanced fibrosis and chronic pancreatitis in the future. On the other side, an imbalance of NO-system in alcoholic rats leads to disruption of the zymogens secretion in the acinar cells and dilatation of the capillary network in islets. Uneven distribution of zymogen granules may lead to their intracellular activation as evidenced by the deformation of acini and focal apoptosis without inflammatory response. In this case, violation of the key adaptive responses in the pancreas makes it more vulnerable to the effects of ethanol, its metabolites, and other environmental factors, and may increase the probability of chronic pancreatitis development. At the same time, forementioned process of cell death in the pancreas is considerably more prolonged, and long term course eliminates the activation of proliferation or functional tissue regeneration.


Ellenrieder, V., Schneiderhan, W., Bachem, M., Adler, G., 2004. Fibrogenesis in the pancreas. Rocz. Akad. Med. Bialymst. 49, 40–46.

Lucas, K., Pitari, G., Kazerounian, S., Ruiz-Stewart, I., Park, J., Schulz, S., Chepenik, K., Waldman, S., 2000. Guanylyl cyclases and signaling by cyclic GMP. Pharmacol. Rev. 52(3), 375–414.

Maev, I.V., Kazjulin, A.N., Samsonov, A.A., Kucherjavyj, J.A., 2006. Hronicheskij pankreatit (algoritm diagnostiki i lechebnoj taktiki). Posobie dlja vrachej obshhej praktiki, terapevtov, gastrojenterologov [Chronic pancreatitis (diagnostic and treatment tactics). Allowance for general practitioners, internists, gastroenterologists]. GOU VUNMC MZiSR RF, Moscow (in Russian).

Morselli-Labate, A.M., Fantini, L., Pezzilli, R., 2007. Hydrogen sulfide, nitric oxide and a molecular mass 66 u substance in the exhaled breath of chronic pancreatitis patients. Pancreatology 7, 497–504. >>doi: 10.1159/000108967

Saluja, A., Lerch, M., Phillips, P., Dudeja, V., 2007. Why does pancreatic overstimulation cause pancreatitis? Annu. Rev. Physiol. 69, 249–269. >>doi: 10.1146/annurev.physiol.69.031905.161253

Sarles, H., Cros, R., Bidart, J., 1979. A multicenter inquiry into the etiology of pancreatic diseases. Digestion 19(2), 110–125. >>doi: 10.1159/000198331

Satoh, A., Gukovskaya, A., Reeve Jr, J., Shimosegawa, T., Pandol, S., 2006. Ethanol sensitizes NF-kappaB activation in pancreatic acinar cells through effects on protein kinase C-varepsilon. Am. J. Physiol. Gastrointest. Liver Physiol. 291(3), 432–438. >>doi: 10.1152/ajpgi.00579.2005

Severina, I.S., 2002. Oksid azota. Rol' rastvorimoj guanilatciklazy v mehanizmah ego fiziologicheskih jeffektov [Nitric oxide. The role of soluble guanylat cyclase in the mechanisms of its physiological effects]. Voprosy Medicinskoj Himii [Problems of Medical Chemistry] 1, 4–30 (in Russian).

Talukdar, R., Saikia, N., Singal, D.K., Tandon, R., 2006. Chronic pancreatitis: Evolving paradigms. Pancreatology 6, 440–449. >>doi: 10.1159/000094561

Tkach, M.N., 2013. Prakticheskie podhody k diagnostike hronicheskogo pankreatita [Practical approaches to the diagnosis of chronic pancreatitis]. Suchasna Gastro-enterologіja [Modern Gastroenterology] 69(1), 136–148 (in Russian).

Vonlaufen, A., Spahr, L., Apte, M.V., 2014. Alcoholic pancreatitis: A tale of spirits and bacteria. World J. Gastrointest. Pathophysiol. 5(2), 82–90.

How to Cite
Oshmyanska, N. Y., Galinsky, A. A., & Gaidar, Y. A. (2014). Peculiarities of death and regeneration of pancreas cells at early stages of alcoholic chronic pancreatitis. Regulatory Mechanisms in Biosystems, 5(2), 138-142.