On the significance of the activity of liver arginase and Kupffer cells in the development of secondary atherogenic dyslipidemia and the formation of thyroid status in rats with experimental peritonitis

Peritonitis is one of the most severe complications of various diseases and injuries of the abdominal organs. The diagnosis of peritonitis in a general sense implies any form and severity of inflammation of the peritoneum. Currently, the problem of peritonitis remains actual, despite the achievements of scientific and technological progress. So, despite the successes of modern surgery, the achievements of asepsis and antiseptics, the rather wide possibilities of antibacterial, infusion and detoxification therapy, the incidence of peritonitis and mortality from it remain at a high level. 

The aim of the study was to elucidate the significance of the activity of liver arginase and Kupffer cells in the development of secondary atherogenic dyslipidemia and the formation of thyroid status in rats with experimental peritonitis.  

It has been established that under conditions of experimental peritonitis in rats, the activity of liver arginase decreases, the content of NO3 – /NO2 – increases and the level of iodine-containing thyroid hormones in the blood decreases, secondary atherogenic dyslipoproteinemia develops. Liver arginase and Kupffer cells are involved in changes in the content of total cholesterol in the liver, total cholesterol, lipoprotein cholesterol, the level of iodine-containing hormones in the blood and body temperature in peritonitis. A decrease in the activity of Kupffer cells in peritonitis is accompanied by an increase in the level of triiodothyronine in the blood, a less pronounced decrease in the activity of liver arginase and a weakening of the development of characteristic changes in the content of total cholesterol in the liver, lipoprotein cholesterol in the blood and prevents the development of secondary dyslipoproteinemia. Depression of liver arginase in conditions of peritonitis aggravates changes in the content of total cholesterol in blood and liver lipoproteins, triiodothyronine in the blood and contributes to the development of secondary dyslipoproteinemia.

1. Gostishchev V. K. Peritonitis. Moscow, Meditsina Publ., 1985. 473 p. (in Russian).

2. Hotchkiss R. S., Karl I. E. The pathophysiology and treatment of sepsis. New England Journal of Medicine, 2003, vol. 348, no. 2, pp. 138–150. https://doi.org/10.1056/NEJMra021333

3. Tomnyuk N. D., Danilina E. P., Chernykh A. N., Parno A. A., Shurka K. S. Peritonitis as one of the main causes of lethal outcomes. Sovremennye naukoemkie tekhnologii [Modern high technologies], 2010, no. 10, pp. 81–84 (in Russian).

4. Abdullaev E. G., Babyshin V. V., Novikov Yu. A., Gusev A. V., Malakhov N. B. Peritonitis. Vladimir, Vladimir State University Publishing House, 2014. 144 p. (in Russian).

5. Gozhenko A. I., Vasil’ev A. A., Nasibullin В. А. Peculiarities of experimental peritonitis in rats by irrigation the abdominal cavity with xenon saturated solution. Svit meditsini ta biologii [The world of medicine and biology], 2014, no. 2 (44), pp. 111–114 (in Russian).

6. Mishnev O. D., Tumanova U. N., Shchegolev A. I. Pathology of the liver in sepsis. Mezhdunarodnyi zhurnal prikladnykh i fundamental’nykh issledovanii [International journal of applied and basic research], 2017, no. 8-2, pp. 267–271 (in Russian).

7. Korotkevich T. V., Vismont F. I. Secondary dyslipoproteinemia and liver dysfunction in experimental endotoxinemia. Zdravookhranenie [Health care], 2006, no. 6, pp. 21–23 (in Russian).

8. Viktorov A. V., Yurkiv V. A. Binding of lipopolysaccharide and complexes of lipopolysaccharide with serum low density lipoproteins to liver macrophages. Biomeditsinskaya khimiya [Biomedical chemistry], 2006, vol. 52, no. 1, pp. 36–43 (in Russian).

9. Chepeleva E. N., Vismont F. I. Peculiarities of blood lipoprotein cholesterol metabolism in rats with experimental peritonitis. BGMU v avangarde meditsinskoi nauki i praktiki: retsenziruemyi ezhegodnyi sbornik nauchnykh trudov. Vypusk 10 [BSMU at the forefront of medical science and practice: a peer-reviewed annual collection of scientific papers. Iss. 10]. Minsk, 2020, pp. 390–394 (in Russian).

10. Zhang C., Wang K., Yang L., Liu R., Chu Y., Qin X., Yang P., Yu H. Lipid metabolism in inflammation-related diseases. Analyst, 2018, vol. 143, no. 19, pp. 4526–4536. https://doi.org/10.1039/c8an01046c

11. Harris H. W., Grunfeld C., Feingold K. R., Rapp J. H. Human very low density lipoproteins and chylomicrons can protect against endotoxininduced death in mice. Journal of Clinical Investigation, 1990, vol. 86, no. 3, pp. 696–702. https:// doi.org/10.1172/JCI114765

12. van der Voort P. H. J., Gerritsen R. T., Bakker A. J., Boerma E. Ch., Kuiper M. A., de Heide L. HDL-cholesterol level and cortisol response to synacthen in critically ill patients. Intensive Care Medicine, 2003, vol. 29, no. 12, pp. 2199–2203. https://doi.org/10.1007/s00134-003-2021-7

13. Vismont F. I., Artyushkevich S. A. On the role of Kupffer cells and hepatocytes in the mechanisms of implementation of triiodothyronine influence on the processes of detoxification and regulation of body temperature. Belorusskii meditsinskii zhurnal [Belarusian medical journal], 2005, vol. 13, no. 3, pp. 45–47 (in Russian).

14. Vismont F. I. Endotoxinemia, dysregulation and the pre-illness formation. Vestsi Natsyyanal’nai akademii navuk Belarusi. Seriya meditsinskikh navuk = Proceedings of the National Academy of Sciences of Belarus. Medical series, 2018, vol. 15, no. 1, pp. 7–16 (in Russian).

15. Mayanskii D. N. Kupffer cells and liver pathology. Patologicheskaya fiziologiya i eksperimental’naya meditsina [Pathological physiology and experimental medicine], 1985, no. 4, pp. 80–86 (in Russian).

16. Sehic E., Hunter W. S., Ungar A. L., Blatteis C. M. Blockade of Kupffer cells prevents the febrile and preoptic prostaglandin E2 responses to intravenous lipopolysaccharide in guinea pigs. Annals of the New York Academy of Sciences, 1997, vol. 813, no. 1, pp. 448–452. https://doi.org/10.1111/j.1749-6632.1997.tb51732.x

17. Volmar B., Rettinger D., Wanner G. A. Modulation of Kupfer cells activity by gadolinium chloride in endotoxemic rats. Shock, 1996, vol. 6, no. 6, pp. 434–441. https://doi.org/10.1097/00024382-199612000-00008

18. Clemente G. S., van Waarde A., Antunes I. F., Dömling A., Elsinga P. H. Arginase as a Potential Biomarker of Disease Progression: A Molecular Imaging Perspective. International Journal of Molecular Sciences, 2020, vol. 21, no. 15, p. 5291. https://doi.org/10.3390/ijms21155291

19. Darcy C. J., Woodberry T., Davis J. S., Piera K. A., McNeil Y. R., Chen Y., Yeo T. W., Weinberg J. B., Anstey N. M. Increased plasma arginase activity in human sepsis: association with increased circulating neutrophils. Clinical Chemistry and Laboratory Medicine, 2014, vol. 52, no. 4, pp. 573–581. https://doi.org/10.1515/cclm-2013-0698

20. Douma C. E., de Waart D. R., Struijk D. G., Krediet R. T. Are phospholipase A2 and nitric oxide involved in the alterations in peritoneal transport during CAPD peritonitis? Journal of Laboratory and Clinical Medicine, 1998, vol. 132, no. 4, pp. 329–340. https://doi.org/10.1016/S0022-2143(98)90047-6

21. Ni J., McLoughlin R. M., Brodovitch A., Moulin P., Brouckaert P., Casadei B., Feron O., Topley N., Balligand J.-L., Devuyst O. Nitric oxide synthase isoforms play distinct roles during acute peritonitis. Nephrology Dialysis Transplantation, 2010, vol. 25, no. 1, pp. 86–96. https://doi.org/10.1093/ndt/gfp415

22. Kelly G. S. Peripheral metabolism of thyroid hormones: a review. Alternative Medicine Review: a Journal of Clinical Therapeutic, 2000, vol. 5, no. 4, pp. 306–333.

23. Mustafina S. V., Rymar O. D., Simonova G. I., Ragino Yu. I., Kuznetsov A. A., Shcherbakova L. V., Malyutina S. K. Functional state of thyroid gland and lipid blood profile. Ateroskleroz [Atherosclerosis], 2010, vol. 6, no. 2, pp. 15–19 (in Russian).

24. Chepeleva E. N., Vismont F. I. Kupffer cells in the regulation of the cholesterol content in the liver and the blood lipoproteins, the level of iodine-containing thyroid hormones in the blood and the body temperature in rats with experimental peritonitis. Vestsi Natsyyanal’nai akademii navuk Belarusi. Seriya meditsinskikh navuk = Proceedings of the National Academy of Sciences of Belarus. Medical series, 2021, vol. 18, no. 4, pp. 391–401 (in Russian).

25. Shapovalova E. Yu., Demyashkin G. A., Malanichev M. Yu., Pogosyan D. A., Zorin I. A., Shchekin V. I. Simulation of experimental sepsis by cecal ligation and puncture (CLP). Ul’yanovskii mediko-biologicheskii zhurnal [Ulyanovsk medical and biological journal], 2020, no. 3, pp. 150–158 (in Russian).

26. Rittirsch D., Huber-Lang M. S., Flierl M. A., Ward P. A. Immunodesign of experimental sepsis by cecal ligation and puncture. Nature Protocols, 2009, vol. 4, no. 1, pp. 31–36. https://doi.org/10.1038/nprot.2008.214

27. Geyer J. W., Dabich D. Rapid method for determination of arginase activity in tissue homogenates. Analytical Biochemistry, 1971, vol. 39, no. 2, pp. 412–417. https://doi.org/10.1016/0003-2697(71)90431-3

28. Burstein M., Samaille J. Sur la clarification du sérum lipémique par l’héparine in vitro. Comptes rendus hebdomadaires des séances de l’Académie des sciences, 1955, vol. 241, no. 9, pp. 664–665.

29. Krekhova M. A., Chekhranova M. K. Fractional determination of cholesterol esters in blood and tissues using thin layer chromatography. Voprosy meditsinskoi khimii [Medicinal chemistry issues], 1971, vol. 17, no. 1, pp. 93–98 (in Russian).

30. Moshage H., Kok B., Huizenga J. R., Jansen P. L. Nitrite and nitrate determinations in plasma: a critical evaluation. Clinical Chemistry, 1995, vol. 41, no. 6, pp. 892–896. https://doi.org/10.1093/clinchem/41.6.892

31. Kamyshnikov V. S., Volotovskaya O. A., Khodyukova A. B., Dal’nova T. S., Vasiliu-Svetlitskaya S. G., Zubovskaya E. T., Alekhnovich L. I. Clinical laboratory research methods. 10th ed. Moscow, MEDpress-inform Publ., 2020. 736 p. (in Russian).

32. Duntas L. H., Mantzou E., Koutras D. A. Circulating levels of oxidized low-density lipoprotein in overt and mild hypothyroidism. Thyroid, 2002, vol. 12, no. 11, pp. 1003–1007. https://doi.org/10.1089/105072502320908349