Assessment of the inflammatory response in the pancreas after administration of N-acetyl cysteine in a model of post-radiation pancreatitis

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Abstract

Introduction. Ionizing radiation can lead to radiation damage to healthy pancreatic tissue, with the development of signs of post-radiation pancreatitis. Electron irradiation potentially has the most “sparing” effect on healthy tissue, but data on this are sparse. The search for means to protect healthy tissues from the effects of ionizing radiation remains relevant. Thus, the use of agents with antioxidant properties (N-acetylcysteine) can potentially slow down the development of post-radiation pancreatitis.

The aim of the study: assessment of the inflammatory response in the pancreas after administration of N-acetylcysteine in a radiation-induced pancreatitis model.

Methods. Wistar rats (n=120) were divided into four groups: I (n=30) – control; II (n=30) – irradiation with electrons in a total irradiation dose of 25 Gy; III (n=30) – pre-irradiation administration of N-acetylcysteine before electron irradiation; IV (n=30) – administration of N-acetylcysteine. Animals were removed from the experiment on the 7th, 30th and 90th days. A morphological assessment of pancreatic fragments and an immunohistochemical study with antibodies to pro- (IL-1, IL-6) and anti-inflammatory (IL-10) cytokines, markers of T-lymphocytes (CD3) and macrophages (CD68) were carried out.

Results. At all stages of the experiment, high levels of expression of pro- and anti-inflammatory cytokines were observed in the electron irradiation group with a slight increase in the number of CD3+ T-lymphocytes and CD68+ macrophages. In the group of pre-radiation administration of N-acetylcysteine, increased levels of immunolabeling were also found when conducting reactions with antibodies to pro- and anti-inflammatory cytokines, however, by the third month of the experiment, practically no CD3+ and CD68+ immunocompetent cells were noted in this group.

Conclusion. Pancreatic local electron irradiation at a total dose of 25 Gy in the early stages leads to the development of a stromal-vascular inflammatory reaction with a capillary-parenchymal block with practically no cellular inflammatory infiltration. At the same time, pre-radiation administration of N-acetylcysteine partially prevents the development of post-radiation pancreatitis.

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About the authors

Grigory Aleksandrovich Demyashkin

Federal State Budgetary Institution “National Medical Research Center of Radiology”; Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Author for correspondence.
Email: dr.dga@mail.ru
ORCID iD: 0000-0001-8447-2600

Doctor of Medical Sciences, Head of the Department of Pathomorphology, Medical Radiological Research Center named after A.F. Tsyba – branch of the Federal State Budgetary Institution “National Medical Research Center of Radiology”, Head of the laboratory of histology and immunohistochemistry of the Institute of Translational Medicine and Biotechnology of the FSAEI HE I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Russian Federation, st. Koroleva, 4, Obninsk, 249036; Trubetskaya st., 8/2, Moscow, 119048

Dmitry Andreevich Atyakshin

RUDN University named after Patrice Lumumba

Email: atyakshin-da@rudn.ru
ORCID iD: 0000-0002-8347-4556

Doctor of Medical Sciences, Director of the Scientific and Educational Resource Center “Innovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis”

Russian Federation, Miklouho-Maklaya st., 6, Moscow, 117198

Dali Ibragimovna Ugurchieva

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: daliyagurchieva@gmail.com
ORCID iD: 0009-0004-7308-8450

Postgraduate Student at the Institute of Translational Medicine and Biotechnology

Russian Federation, Trubetskaya st., 8/2, Moscow, 119048

Vladislav Andreevich Yakimenko

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: Yavladislav87@gmail.com
ORCID iD: 0000-0003-2308-6313

Postgraduate Student at the Institute of Translational Medicine and Biotechnology

Russian Federation, Trubetskaya st., 8/2, Moscow, 119048

Matvey Anatolyevich Vadyukhin

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: vma20@mail.ru
ORCID iD: 0000-0002-6235-1020

Student of the Institute of Clinical Medicine named after N.V. Sklifosovsky

Russian Federation, Trubetskaya st., 8/2, Moscow, 119048

Sergey Nikolaevich Koryakin

Federal State Budgetary Institution “National Medical Research Center of Radiology”

Email: korsernic@mail.ru
ORCID iD: 0000-0003-0128-4538

Candidate of Biological Sciences, Head of the Department of Radiation Biophysics of the Medical Radiological Research Center named after A.F. Tsyba

Russian Federation, st. Koroleva, 4, Obninsk, 249036

References

  1. Seifert L., Werba G., Tiwari S., Giao Ly N.N., Nguy S., Alothman S., Alqunaibit D., Avanzi A., Daley D., Barilla R., Tippens D., Torres-Hernandez A., Hundeyin M., Mani V.R., Hajdu C., Pellicciotta I., Oh P., Du K., Miller G. Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice. Gastroenterology. 2016; 150 (7): 1659–72.e5. doi: 10.1053/j.gastro.2016.02.070
  2. Schröter P., Hartmann L., Osen W., Baumann D., Offringa R., Eisel D., Debus J., Eichmüller S.B., Rieken S. Radiation-induced alterations in immunogenicity of a murine pancreatic ductal adenocarcinoma cell line. Sci Rep. 2020; 10 (1): 686. doi: 10.1038/s41598-020-57456-2
  3. Wydmanski J., Polanowski P., Tukiendorf A., Maslyk B. Radiation-induced injury of the exocrine pancreas after chemoradiotherapy for gastric cancer. Radiother Oncol. 2016; 118 (3): 535–9. doi: 10.1016/j.radonc.2015.11.033
  4. Baek J.Y., Lim D.H., Oh D., Nam H., Kim J.J., Lee J.H., Min B.H., Lee H. Increased Risk of Diabetes after Definitive Radiotherapy in Patients with Indolent Gastroduodenal Lymphoma. Cancer Res Treat. 2022; 54 (1): 294–300. doi: 10.4143/crt.2021.073
  5. Mercantepe F., Tümkaya L., Mercantepe T., Yilmaz Rakici S. The effects of coenzyme Q10 (CoQ10) on ionizing radiation-induced pancreatic β-cell injury. Endocrinol Res Pract. 2023; 27 (3): 127–34. doi: 10.5152/erp.2023.23245
  6. Leung P.S., Chan Y.C. Role of oxidative stress in pancreatic inflammation. Antioxid Redox Signal. 2009; 11 (1): 135–65. doi: 10.1089/ars.2008.2109
  7. Bacarella N., Ruggiero A., Davis A.T., Uberseder B., Davis M.A., Bracy D.P., Wasserman D.H., Cline J.M., Sherrill C., Kavanagh K. Whole Body Irradiation Induces Diabetes and Adipose Insulin Resistance in Nonhuman Primates. Int. J. Radiat Oncol. Biol. Phys. 2020; 106 (4): 878–86. doi: 10.1016/j.ijrobp.2019.11.034
  8. Schoonbroodt D., Zipf A., Hermann G., Jung M. Histological findings in chronic pancreatitis after abdominal radiotherapy. Pancreas. 1996; 12: 313–5.
  9. Демяшкин Г.А., Дубовая Т.К., Угурчиева Д.И., Вадюхин М.А., Ахмедова П.С., Симагина В.К. Морфофункциональная характеристика поджелудочной железы после введения N-ацетилцистеина в модели острого постлучевого панкреатита. Морфология. 2023; 161 (2): 15–22. doi: 10.17816/morph.623166. [Demyashkin G.A., Dubovaya T.K., Ugurchieva D.I., Vadyukhin M.A., Akhmedova P.S., Simagina V.K. Morphofunctional characteristics of the pancreas after N-acetylcysteine administration in an acute postradiation pancreatitis model. Morphology 2023; 161 (2): 15–22. DOI:10 .17816/morph.623166 (in Russian)]
  10. Calvo F.A., Serrano J., Cambeiro M., Aristu J., Asencio J.M., Rubio I., Delgado J.M., Ferrer C., Desco M., Pascau J. Intra-Operative Electron Radiation Therapy: An Update of the Evidence Collected in 40 Years to Search for Models for Electron-FLASH Studies. Cancers (Basel). 2022; 14 (15): 3693. doi: 10.3390/cancers14153693
  11. Zhou R., Bu W., Fan Y., Du Z., Zhang J., Zhang S., Sun J., Li Z., Li J. Dynamic Changes in Serum Cytokine Profile in Rats with Severe Acute Pancreatitis. Medicina (Kaunas). 2023; 59 (2): 321. doi: 10.3390/medicina59020321
  12. Attia A.A., Hamad H.A., Fawzy M.A., Saleh S.R. The Prophylactic Effect of Vitamin C and Vitamin B12 against Ultraviolet-C-Induced Hepatotoxicity in Male Rats. Molecules. 2023; 28 (11): 4302. doi: 10.3390/molecules28114302
  13. Topcu A., Mercantepe F., Rakici S., Tumkaya L., Uydu H.A., Mercantepe T. An investigation of the effects of N-acetylcysteine on radiotherapy-induced testicular injury in rats. Naunyn Schmiedebergs Arch Pharmacol. 2019; 392 (2): 147–57. doi: 10.1007/s00210-018-1581-6
  14. Sia J., Szmyd R., Hau E., Gee H.E. Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer. Front Cell Dev Biol. 2020; 8: 41. doi: 10.3389/fcell.2020.00041
  15. Jiao Y., Cao F., Liu H. Radiation-induced Cell Death and Its Mechanisms. Health Phys. 2022; 123 (5): 376–86. doi: 10.1097/HP.0000000000001601
  16. Moustafa E.M., Moawed F.S.M., Abdel-Hamid G.R. Icariin Promote Stem Cells Regeneration and Repair Acinar Cells in L-arginine / Radiation -Inducing Chronic Pancreatitis in Rats. Dose Response. 2020; 18 (4): 1559325820970810. doi: 10.1177/1559325820970810
  17. Fertey J., Thoma M., Beckmann J., Bayer L., Finkensieper J., Reißhauer S., Berneck B.S., Issmail L., Schönfelder J., Casado J.P., Poremba A., Rögner F.H., Standfest B., Makert G.R., Walcher L., Kistenmacher A.K., Fricke S., Grunwald T., Ulbert S. Automated application of low energy electron irradiation enables inactivation of pathogen- and cell-containing liquids in biomedical research and production facilities. Sci Rep. 2020; 10 (1): 12786. doi: 10.1038/s41598-020-69347-7
  18. Cameron S., Schwartz A., Sultan S., Schaefer I.M., Hermann R., Rave-Fränk M., Hess C.F., Christiansen H., Ramadori G. Radiation-induced damage in different segments of the rat intestine after external beam irradiation of the liver. Exp. Mol. Pathol. 2012; 92 (2): 243–58. doi: 10.1016/j.yexmp.2011.11.007
  19. Bertho A., Iturri L., Brisebard E., Juchaux M., Gilbert C., Ortiz R., Sebrie C., Jourdain L., Lamirault C., Ramasamy G., Pouzoulet F., Prezado Y. Evaluation of the Role of the Immune System Response After Minibeam Radiation Therapy. Int. J. Radiat Oncol. Biol. Phys. 2023; 115 (2): 426–39. doi: 10.1016/j.ijrobp.2022.08.011
  20. Wang Z., Shen L., Wang J., Shan B., Zhang L., Lu F., Guo X., Li X. Immunostimulatory effect of a composition isolated from white peony root oral liquid in the treatment of radiation-induced esophagitis. Exp Ther Med. 2013; 6 (4): 1010–4. doi: 10.3892/etm.2013.1227
  21. Lin L., Xie S., Zhao Y., Liang Z., Wu Q., Fang M., Teng X., Shi B., Yang Y., Chen B. Ultrasound-induced destruction of heparin-loaded microbubbles attenuates L-arginine-induced acute pancreatitis. Eur. J. Pharm Sci. 2023; 180: 106318. doi: 10.1016/j.ejps.2022.106318
  22. Lu C.L., Wang Y., Yuan L., Li Y., Li X.Y. The angiotensin-converting enzyme 2/angiotensin (1–7)/Mas axis protects the function of pancreatic β cells by improving the function of islet microvascular endothelial cells. Int. J. Mol. Med. 2014; 34 (5): 1293–300. doi: 10.3892/ijmm.2014.1917
  23. Mercantepe F., Topcu A., Rakici S., Tumkaya L., Yilmaz A. The effects of N-acetylcysteine on radiotherapy-induced small intestinal damage in rats. Exp Biol Med (Maywood). 2019; 244 (5): 372–9. doi: 10.1177/1535370219831225
  24. Mansour H.H., Hafez H.F., Fahmy N.M., Hanafi N. Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats. Biochem Pharmacol. 2008; 75 (3): 773–80. doi: 10.1016/j.bcp.2007.09.018

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2. Fig. 1. Pancreas of the control and experimental groups. Top – immunohistochemical reactions with antibodies to IL-1β, ×400. Below is the distribution of expression of pro- (IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines in the endocrine cells of the pancreatic islets in the first week, first month and third month of the experiment, %

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3. Fig. 2. Pancreas of the control and experimental groups in the third month of the experiment; immunohistochemical study, ×400. Top row – antibodies to CD3 (T-lymphocytes). Bottom row – antibodies to CD68 (macrophages)

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