Morphological evaluation of the effects of ursodeoxycholic acid on muscular layer of the gallbladder wall of the mice

Authors

DOI:

https://doi.org/10.26641/1997-9665.2020.2.7-16

Keywords:

ultrastructure, smooth muscle cells, fibroblasts, gallbladder, mice, ursodeoxycholic acid

Abstract

Background. Significant prevalence and the possibility of transformation into organic pathology determine the relevance of functional disorders of the gallbladder and sphincter of Oddi in children. The proposed hypothesis is that the increased differentiation of fibroblasts into the smooth muscle cells of the gallbladder wall in the experimental model of mice occurs under the influence of ursodeoxycholic acid. Objective: to determine the histo-ultrastructural changes of cells of the muscular wall of the gallbladder wall of experimental mice under the action of ursodeoxycholic acid. Methods. By the method of simple randomization, mice were divided into 2 groups: experimental group (n = 17) - animals that were received ursodeoxycholic acid at a dose of 100.0 mg/kg and control group (n = 13) - intact (distilled water). Gallbladder morphological examination was performed using light and electron microscopy methods. Results. Impact of ursodeoxycholic acid on the gallbladder muscular layer characterized by moderate hypertrophy of the gallbladder smooth muscle myocytes that contain metabolically active pale nuclei and prominent nucleoli. After the ursodeoxycholic acid administration an increase in the content and activity of the elements of the contractile and energy apparatus of leiomyocytes were found. In addition, ursodeoxycholic acid administration led to an increase in the number of caveolae and micropinocytic vesicles near the cell membrane of smooth muscle cells. Analysis of the components of the interstitium of the mice gallbladder muscular layer of the experimental group revealed the nuclear activity of fibroblasts due to the decondensation of chromatin. Also in the experimental group was characterized by the presence of immature collagen fibrils along with normal striated fibers that was a sign of the rearrangement of the endomysium structure. Conclusion. The effect of ursodeoxycholic acid on the muscular membrane of the gallbladder wall of mice of the experimental group is morphologically manifested by signs of moderate hypertrophy of smooth myocytes, activation of their intracellular transport and increased activity of interstitial fibroblasts.

References

  1. Unified clinical protocol of medical aid for children with diseases of the digestive system: Order of the Ministry of Health of Ukraine № 59 dated January 29, 2013 // Modern Pediatrics. 2013;4:20-31. Ukrainian.
  2. Shadrin OG, Chernega NF. [Microbiota and diseases of the hepatobiliary system: new opportunities in the treatment of young children]. Child health. 2015;65(5):23-9. Ukrainian.
  3. Shutova EV, Belousova OY, Pavlenko NV. [Optimization of diagnosis of early stage of gallstone disease in children]. Modern pediatrics. 2015;66(2):88-91. Ukrainian.
  4. Volosoveс OP, Zubarenko OV, Kryvopustov SP ta іn. [Pediatrics (Gastroenterology and Pathology of the Early Age): Teach. Manual.] Odessa: Printing house, Printing South. 2017:165-80. Ukrainian.
  5. Abaturov AE, Zavhorodnia NYu, Babich VL. [MicroRNA for diseases of the hepatobiliary system]. Dnipro: TOV "DOMINANTA PRINT". 2018:336. Russian.
  6. Hayes CN, Chayama K. MicroRNAs as Biomarkers for Liver Disease and Hepatocellular Carcinoma. Int. J. Mol. Sci. 2016 Feb 24:17(3);280. doi:10.3390/ijms17030280
  7. Letelier P, Riquelme I, Hernández AH at al. Circulating MicroRNAs as Biomarkers in Biliary Tract Cancers. Int J Mol Sci. 2016 May:17(5):791. doi:10.3390/ijms17050791
  8. Sakamoto T, Morishita A, Nomura T, Tani J, Miyoshi H at al. Identification of microRNA pro-files associated with refractory primary biliary cir-rhosis. Mol. Med. Rep. – 2016 Oct;14(4):3350-6. doi: 10.3892/mmr.2016.5606
  9. Rodrigues PM, Afonso MB, Simão AL. miR-21 ablation and obeticholic acid ameliorate nonalcoholic steatohepatitis in mice. Cell Death Dis. 2017;8(4):e2748. doi: 10.1038/cddis.2017.172
  10. Kim DJ, Chung H, Ji SC et al. Ursodeoxycholic acid exerts hepatoprotective effects by regulating amino acid, flavonoid, and fatty acid metabolic pathways. Metabolomics. 2019;15:30. Doi: 10.1007/s11306-019-1494-5
  11. Abaturov OE, Babich VL. [Drug modulation of activity of microRNA generation in functional disorders of the gallbladder and Oddi's sphincter in children]. Child's Health. 2019;2(14):53-9. doi: 10.22141/2224-0551.14.2.2019.165544. Ukrainian.
  12. Abaturov AE, Vysochyna IL, Babych VL, Dosenko VE. Regulation of microRNA expression level by choleretic therapy in functional disorders of the gallbladder and Оddi's sphincter in children. Wiadomości Lekarskie. 2020;73(1):41-5. - DOI: 10.36740/WLek202001107
  13. Krist B, Florczyk U, Pietraszek-Gremplewicz K, Józkowicz A, Dulak J. The Role of miR-378a in Metabolism, Angiogenesis, and Muscle Biology. International Journal of Endocrinology. 2015;Article ID 281756:13 p. doi:10.1155/2015/281756
  14. Zhang T, Hu J, Wang X, Zhao X, Li Zh, Niu J at al. MicroRNA-378 promotes hepatic inflammation and fibrosis via modulation of the NF-jB-TNFa pathway. Journal of Hepatology. 2019;70:87–96. Doi: 10.1016/j.jhep.2018.08.026
  15. Gagan J, Dey BK, Layer R, Yan Z, Dutta A. MicroRNA-378 targets the myogenic repressor MyoR during myoblast differentiation. J Biol Chem. 2011;286(22):19431-8. doi: 10.1074/jbc.M111.219006
  16. European Convention for the Protection of Vertebrate Animals Used for Experimental and Oth-er Scientific Purposes. 1986. European Treaty Series 123. Strasbourg, France: Council of Europe.
  17. Law of Ukraine. On the protection of animals from cruelty [Electronic resource]. Information of the Verkhovna Rada of Ukraine (VVR). 2006. Access mode: http://zakon1.rada.gov.ua/laws/show/3447-15. Ukrainian.
  18. Sarkisov DS, Perova YL. Microscopic technique. Moscow: Medicine; 1996. 542p. Russian.
  19. Tverdokhlib IV, Petruk NS, Ivanchenko MV, Silkina JuV, Khripkov IS, Pertseva NO, Shevchenko KM, Goodlett TO, Malkov II, Berehovenko IM, Zinenko DYu, Galaida NO, Varin VV, inventors; State Institution «Dnipropetrovsk medical academy of the Health Ministry of Ukraine». Method of determining the coordinates of ultrastructures in transmission electron microscopy of biological objects. Ukrainian patent UA 83611. 2013 Sep 25. Int. CI. G01N 1/28. Ukrainian.
  20. Kuo J. Electron microscopy: methods and protocols. Totowa, New Jersey: Humana Press Inc, 2007. 608 p.

How to Cite

Abaturov, A. E., Babуch V. L., Bondarenko, N. S., Bondarenko, O. O., Lievykh, A. E., & Tverdokhlib, I. V. (2020). Morphological evaluation of the effects of ursodeoxycholic acid on muscular layer of the gallbladder wall of the mice. Морфологія / Morphologia / Morfologìâ, 14(2), 7–16. https://doi.org/10.26641/1997-9665.2020.2.7-16

Issue

Section

Статті