DYNAMICS OF ULTRASTRUCTURAL CHANGES OF THE COMPONENTS IN THE WALL OF COMMON BILE DUCT DURING THE LONG-TERM INFLUENCE OF OPIOID IN THE EXPERIMENT

Mateshuk-Vatseba L. R., Hirniak І. І.

MORPHOLOGY

Scentific article

The article is devoted to the topical problem of modern medicine – the influence of opioids on the structural organization of organs. Information in the professional literature on this problem is insufficient and often contradictoryThe study aimed to establish the features of changes in the ultrastructure of the common bile duct wall in the dynamics of long-term experimental effects of opioid for creation of the morphological basis for the development of methods for preventing structural changes in the bile ducts for using narcotic agents. The study was performed on 24 adult white male rats, aged 4.5-5.5 months and weighing 180-220 g. Administration of nalbuphine was performed intramuscularly, according to the following scheme: I week – 8 mg/kg, II week – 15 mg/kg, III week – 20 mg/kg, IV week – 25 mg/kg, V week – 30 mg/kg, VI week – 35 mg/kg. The method of electron microscopy was used. The study and photographing of the material were performed using a microscope UEMV-100 K at an acceleration voltage of 75 kV and magnifications on the microscope screen of 1000-12000 x. The results of the study allowed us to obtain new data on changes in the ultrastructure of the common bile duct wall at different times (after 2, 4, and 6 weeks) of the opioid effect. The first changes in the ultrastructural organization of the common bile duct wall are developed after two weeks of Nalbuphine administration to white rats and manifested by signs of microvascular angiopathy, edema of the own plate in the mucous membrane and connective tissue layers between the bundles of smooth myocytes of the duct muscular membrane. Angiopathy was evidenced by changes in all parts of the hemomicrocirculatory tract. Capillaries had an enlarged lumen filled with altered shape (dumbbell-shaped) erythrocytes and blood plasma, the endothelial cell nuclei lost their proper shape, the nuclear membrane formed deep intussusception, condensed chromatin was mainly distributed along the nuclear membrane; on the periphery, the cytoplasm of some endotheliocytes is expanded, others are indurated in the form of a strip, contained many micropinocytic vesicles, formed cytoplasmic growths in the lumen of the vessel, mitochondria have a weak electron density due to edema, there are visible single dilated cristae. The long-term effect of opioid caused profound destructive changes in cellular elements (cholangiocytes, glandular epitheliocytes, smooth myocytes) of the common bile duct wall, in particular, loss of proper cell shape, karyopyknosis and karyorrhexis of their nuclei; edema and enlightenment of cytoplasma, development of small vacuole dystrophy of cells, and organelle fragmentation. The mitochondrial apparatus and the granular endoplasmic reticulum of cholangiocytes were particularly affected. Mitochondria have the swollen matrix and destroyed crystals, membranes of some mitochondria are intermittent, cristae are damaged, many mitochondria turned into large vacuoles, a granular endoplasmic reticulum is destructured, fragments of granular endoplasmic reticulum are hypertrophied, its cisterns are expanded, in some places merged, forming unstructured areas. Paranuclear and paracellular edema developed, intercellular contacts were broken. After six weeks of Nalbuphine administration to experimental animals, the disorganization of connective tissue elements indicated the development of fibrosis of the common bile duct wall. The presented data are the basis for further research by morphologists and clinicians to develop new methods for the diagnosis, prevention, and treatment of bile duct diseases in drug addicts and patients who are forced to take opioids for a long time

common bile duct, ultrastructure, opioid, experiment.

1. Baumeister D, Tojo LM, Tracy DK. Legal highs: staying on top of the flood of novel psychoactive substances. Ther Adv Psychopharmacol. 2015;5(2):97-132. DOI: 10.1177/2045125314559539
2. Soleimanpour H, Safari S, Shahsavari Nia K, Sanaie S, Alavian SM. Opioid Drugs in Patients With Liver Disease: A Systematic Review. Hepat Mon. 2016;16(4):e32636. DOI: 10.5812/hepatmon.32636
3. DeAngelis C, Marietti M, Bruno M, Pellicano R, Rizzetto M. Endoscopic ultrasound in common bile duct dilatation with normal liver enzymes. World J Gastrointest Endosc. 2015 Jul 10;7(8):799-805. DOI: 10.4253/wjge.v7.i8.799
4. Kim HY, Yang HK, Kim SH, Park JH. Ibuprofen Associated Acute Vanishing Bile Duct Syndrome and Toxic Epidermal Necrolysis in an Infant. Yonsei Med J. 2014;55(3):834-7. DOI: 10.3349/ymj.2014.55.3.834
5. Al-Nowfal A, Al-Abed YA. Chronic biliary colic associated with ketamine abuse. Int Med Case Rep J. 2016;9:135-7. DOI: 10.2147/IMCRJ. S100648
6. Cheung AC, Pisarello MJ, LaRusso NF. Pathobiology of biliary epithelia. Biochim Biophys Acta. 2018;1864(4PtB):1220-31. DOI: 10.1016/j. bbadis.2017.06.024
7. Franchitto A, Onori P, Renzi A, Carpino G, Mancinelli R, Alvaro D, Gaudio E. Recent advances on the mechanisms regulating cholangiocyte proliferation and the significance of the neuroendocrine regulation of cholangiocyte pathophysiology. Ann Transl Med. 2013;1(3):27. DOI: 10.3978/j.issn.2305-5839.2012.10.03
8. Amaya MJ, Nathanson MH. Calcium signaling and the secretory activity of bile duct epithelia. Cell Calcium. 2014;55(6):317-24. DOI: 10.1016/j.ceca.2014.02.003
9. Sundaram V, Björnsson ES. Drug-induced cholestasis. Hepatol Commun. 2017;1(8):726-35. DOI:
10. 1002/hep4.1088 10. Mateshuk-Vatseba L, Kost A, Pidvalna U. Effect of Narcotic Analgesics on the Ultrastructure of the Eyeball (Experimental Study). Journal of Morphological Sciences. Georg Thieme Verlag KG; 2018 Dec 35(04):251-4. Available from: http://dx.doi.org/10.1055/s-0038-1676543
11. Giusto M, Barberi L, Di Sario F, Rizzuto E, Nicoletti C, Ascenzi F, et al. Skeletal muscle myopenia in mice model of bile duct ligation and carbon tetrachloride-induced liver cirrhosis. Physiol Rep. 2017;5(7):e13153. DOI: 10.14814/phy2.13153
12. Hargrove L, Graf-Eaton A, Kennedy L, Demieville J, Owens J, Hodges K, et al. Isolation and characterization of hepatic mast cells from cholestatic rats. Lab Invest. 2016;96(11):1198-210. DOI: 10.1038/labinvest.2016.89
13. Joshi N, Ray JL, Kopec AK, Luyendyk JP. Dose-Dependent Effects of Alpha-Naphthylisothiocyanate Disconnect Biliary Fibrosis from Hepatocellular Necrosis. J Biochem Mol Toxicol. 2017;31(1):1-7. DOI: 10.1002/jbt.21834
14. Sheen JM, Chen YC, Tain YL, Huang LT. Increased Circulatory Asymmetric Dimethylarginine and Multiple Organ Failure: Bile Duct Ligation in Rat as a Model. Int J Mol Sci. 2014;15(3):3989-4006. DOI: 10.3390/ijms15033989
15. Vartak N, Damle-Vartak A, Richter B, Dirsch O, Dahmen U, Hammad S, Hengstler JG. Cholestasis-induced adaptive remodeling of interlobular bile ducts. Hepatology. 2016;63(3):951-64. DOI: 10.1002/hep.28373
16. Grammatikopoulos T, Sambrotta M, Strautnieks S, Foskett P, Knisely AS, Wagner B, et al. Mutations in DCDC2 (doublecortin domaincontaining protein 2) in neonatal sclerosing cholangitis. J Hepatol. 2016;65(6):1179-87. DOI: 10.1016/j.jhep.2016.07.017
17. Leonhardt S, Veltzke-Schlieker W, Adler A, Schott E, Hetzer R, Schaffartzik W, et al. Trigger mechanisms of secondary sclerosing cholangitis in critically ill patients. Crit Care. 2015;19(1):131. DOI: 10.1186/s13054-015-0861-5

«Bulletin of problems biology and medicine» Issue 3 (157), 2020 year, 237-241 pages, index UDK 611.367-018.1:615.212.7]-08

10.29254/2077-4214-2020-3-157-237-241