S. Chooklin, S. Chuklin, G. Shershen
Lviv Regional Clinical Hospital
Introduction. The pathogenesis of acute pancreatitis (AP) continues to be a mystery to scientists. However, significant achievements in the field of fundamental research in the last decade have improved the information on pathophysiological processes in the AP. However, despite the progress in understanding early events in AP, addi tional research is needed to quickly and accurately predict the severe course of the disease, as well as more specif ic and purposeful treatment. Indispensable help in this issue is to study the pathogenesis of AP in an experiment in laboratory animals.
The aim of the study. Determine the features of inflammatory processes, oxidative and nitrosative stress in Lornithineinduced acute pancreatitis.
Materials and methods. Experiment was conducted on 32 white rats of the Wistar line. Rats were divided into two groups: 1 with induced acute necrotizing pancreatitis (16 rats), 2 control (16 intact animals). Acute pancre atitis was caused by intraperitoneal injection of Lornithine (3 g/kg). They conducted a biochemical study, as well as determination of indicators of inflammation, oxidative/nitrosative stress in blood serum and pancreatic tissue. The statistical calculation of the indicators was carried out using nonparametric methods.
Results. At experimental AP in rats in the tissue of software significantly (an average of 2.99 times) increased activity of myeloperoxidase (MPO). In this case, the level of Pamylase in serum of blood rats with AP increased by 270.45 %. It was noted that the activity of MPO in the rat’s soft tissue was probably correlated with the concentration of Pamylase in serum. In rats with acute pancreatitis, the activity of inducible (calciumindependent) de novo synthesis of NO increased by 1.9 times compared with the group of intact rats (p = 0.000913). At the same time, activity of calciumdependent NOsynthase in the tissue of software practically did not change. The proportion of physiological constitutive synthesis of NO (oxidic metabolism of Larginine by percentage of cNOS) in the diet of practically healthy rats was, on average, 51.78 ± 4.38 %, whereas in rats with AP, there was a marked decrease of this indicator up to 37.38 ± 5.85 %. According to the results of experimental data, it was determined that the activity of MPO in the software substantially correlated with the activity of iNOS and inversely with the proportion of cNOS, which indicates an increase in the synthesis of pathological NO in the intensification of the inflammatory process in rats at the AP. At the same time, almost the same correlation is determined between the level of Pamylase in blood serum of rats with activity of iNOS (p = 0.000255) and the share of cNOS (p = 0.000015) in the tissue of the software.
H2S significantly lowered in Lornithineinduced pancreatitis in rats to 71.71 ± 7.83 mmol/L (in intact rats 91.98 ± 3.22 mmol/L) (p = 0.000004). At the same time, the concentration of H2S significantly correlated inversely with MPO activity in the tissue (p = 0.000005) and iNOS (p = 0.000098), serum Pamylase concentration (p = 0.000001). With the decrease in the level of H2S in serum, the proportion of physiological constitutive synthesis of NO in the software decreased (p = 0.000139).
Conclusions. The obtained results of the experiment indicate a significant importance in the pathogenesis of AP oxidative and nitrosative stress, lack of synthesis of physiological gasotransmitters.
- Bondarchuk T. Influence of vitamins C and E on lipoperoxidation processes and activity of the NO-synthase system in pancreatic gland of rats on the background of adrenalin-induced stress. Bukovinsky Medical Bulletin. 2014;18(2):14-17. (Ukrainian).
- Yaremchuk O. Investigation of the concentration of nitrite anion and proinflammatory cytokines in acute experimental pancreatitis and the action of the modulator of nitric oxide synthesis. Medical Chemistry. 2013;15(40):89-95. (Ukrainian).
- Abogresha NM, Greish SM, Abdelaziz EZ, Khalil WF. Remote effect of kidney ischemia-reperfusion injury on pancreas: role of oxidative stress and mitochondrial Arch Med Sci. 2016;12(2):252-262. https://doi.org/10.5114/aoms.2015.48130
- Agarwal S,George J, Padhan RK, Vadiraja PK, Behera S, Hasan A et al. Reduction in mortality in severe acute pancreatitis: A time trend analysis over 16 years. 2016;16(2):194-199. https://doi.org/10.1016/j.pan.2016.01.012
- Alipour A, Ribalta J, Njo TL, Janssen HW, Birnie E, van Miltenburg AJ et al. Trans-vessel gradient of myeloperoxidase in coronary artery disease. Eur J Clin Invest. 2013;43(9):920-925. https://doi.org/10.1111/eci.12121
- Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MGet al. Classification of acute pancreatitis-2012: revision of the Atlanta classification and definitions by international consensus. 2013;62(1):102-111. https://doi.org/10.1136/gutjnl-2012-302779
- Bradley PP, Christensen RD, Rothstein G. Cellular and extracellular myeloperoxidase in pyogenic. Blood. 1982;60(3):618-622.
- Chakraborty M, Hickey AJ, Petrov MS, Macdonald JR, Thompson N, Newby L et al. Mitochondrial dysfunction in peripheral blood mononuclear cells in early experimental and clinical acute Pancreatology. 2016;16(5):739-747. https://doi.org/10.1016/j.pan.2016.06.659
- Chan MV, Wallace JL. Hydrogen sulfide-based therapeutics and gastrointestinal diseases: translating physiology to Am J Physiol Gastrointest Liver Physiol. 2013;305(7):G467-73. https://doi.org/10.1152/ajpgi.00169.2013
- Chin SY, Pandey KN, Shi SJ, Kobori H, Moreno C, Navar LG. Increased activity and expression of Ca(2+)-dependent NOS in renal cortex of ANG II-infused hypertensive Am J Physiol. 1999;277(5):F797-804. https://doi.org/10.1152/ajprenal.1999.277.5.F797
- Gotoh T, Mori M. Nitric oxide and endoplasmic reticulum stress. Arterioscler Thromb Vasc Biol. 2006;26(7):1439-1446. https://doi.org/10.1161/01.ATV.0000223900.67024.15
- Habtezion A. Inflammation inacute and chronic Curr Opin Gastroenterol. 2015;31(5):395-399. https://doi.org/10.1097/MOG.0000000000000195
- Han X, Wang Y, Chen H, Zhang J, Xu C, Li J, Li M. Enhancement of ICAM-1 via the JAK2/STAT3 signaling pathway in a rat model of severe acute pancreatitis-associated lung injury. Exp Ther Med. 2016;11(3):788-796. https://doi.org/10.3892/etm.2016.2988
- Jakkampudi A, Jangala R, Reddy BR, Mitnala S, Nageshwar Reddy D, Talukdar R. NF-κB in acute pancreatitis: Mechanisms and therapeutic Pancreatology. 2016;16(4):477-488. https://doi.org/10.1016/j.pan.2016.05.001
- Jiang CY, Wang W. Resistin aggravates the expression of proinflammatory cytokines in cerulein stimulated AR42J pancreatic acinar cells. Mol Med Rep. 2017;15(1):502-506. https://doi.org/10.3892/mmr.2016.6027
- Kolarova H, Klinke A, Kremserova S, Adam M, Pekarova M, Baldus S et al. Myeloperoxidase induces the priming of platelets. Free Radic Biol Med. 2013;61:357-369. https://doi.org/10.1016/j.freeradbiomed.2013.04.014
- Li H, Liu J, Wang W, Zhang Z, Li D, Lin K et al. Matrix metalloproteinase 9 and vasodilator-stimulated phosphoprotein related to acute kidney injury in severe acute pancreatitis Dig Dis Sci. 2015;60(12):3647-3655. https://doi.org/10.1007/s10620-015-3820-8
- Merza M, Hartman H, Rahman M, Hwaiz R, Zhang E, Renström E et al. Neutrophil extracellular traps induce trypsin activation, inflammation, and tissue damage in mice with severe acute Gastroenterology. 2015;149(7):1920-1931.e8. https://doi.org/10.1053/j.gastro.2015.08.026
- Mullane KM, Kraemer R, Smith B. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Methods. 1985;14(3):157-167. https://doi.org/10.1016/0160-5402(85)90029-4
- Pendharkar SA, Singh RG, Petrov MS. Cross-talk between innate cytokines and the pancreatic polypeptide family in acute pancreatitis. 2017;90:161-168. https://doi.org/10.1016/j.cyto.2016.11.014
- Pérez S, Pereda J, Sabater L, Sastre J. Redox signaling in acute pancreatitis. Redox Biol. 2015;5:1-14. https://doi.org/10.1016/j.redox.2015.01.014
- Rakonczay Z Jr, Hegyi P, Dósa S, Iványi B, Jármay K, Biczó G et al. A new severe acute necrotizing pancreatitis model induced by L-ornithine in Crit Care Med. 2008;36(7):2117-2127. https://doi.org/10.1097/CCM.0b013e31817d7f5c
- Salter M, Knowles RG, Moncada S. Widespread tissue distribution, species and changes in activity of Ca2+-dependent and Ca2+-independent nitric oxide. FEBS Lett. 1991;291(1):145-149. https://doi.org/10.1016/0014-5793(91)81123-P
- Svenson A. А rapid and sensitive spectrophotometric method for determination of hydrogen sulfide with 2,2′-dipyridyl disulfidе. Anal Biochem. 1980;107(1):51-55. https://doi.org/10.1016/0003-2697(80)90490-X
- Tejero J, Shiva S, Gladwin MT. Sources of VascularNitric Oxide and Reactive Oxygen Species and Their Regulation. 2019;99(1):311-379. https://doi.org/10.1152/physrev.00036.2017
- Tomkötter L, Erbes J, Trepte C, Hinsch A, Dupree A, Bockhorn M et al. The effects of pancreatic microcirculatory disturbances on histopathologic tissue damage and the outcome in severe acute pancreatitis. 2016;45(2):248-253. https://doi.org/10.1097/MPA.0000000000000440
- Wu JS, Li WM, Chen YN, Zhao Q, Chen QF. Endoplasmic reticulumstress is activated in acute J Dig Dis. 2016;17(5):295-303. https://doi.org/10.1111/1751-2980.12347
- Zhu H, Huang L, Zhu S, Li X, Li Z, Yu C, Yu X. Regulation of autophagy by systemic admission of microRNA-141 to target HMGB1 in l-arginine-induced acute pancreatitis in vivo. Pancreatology. 2016;16(3):337-346. https://doi.org/10.1016/j.pan.2016.03.004