Features of the structural organization of the interlobular bile ducts under conditions of prolonged exposure to opioids in the experiment

  • L. R. Mateshuk-Vatseba Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
  • I. I. Hirniak Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
Keywords: interlobular bile ducts, microstructure, opioid, experiment.


The article contains new information on the current problem of the influence of endo- and exopathogenic factors on the structure of the digestive system. The purpose of the study was to establish the structural features of the interlobular bile ducts under the conditions of six weeks of exposure to nalbuphine in the experiment. The study was based on 30 white laboratory rats of male reproductive age. Histological sections of the liver were stained with hematoxylin and eosin according to conventional methods. The «Aver Media» computer system was used to photograph the micropreparations. The computer program ImageJ was used to measure the diameter of the lumen and the wall thickness of the interlobular bile duct. «Excel» and «Statistica» 6.0 software were used for statistical processing of the obtained digital data. The results of the study show that against the background of nalbuphine administration for six weeks there are morphological changes in the interlobular bile ducts of experimental animals, manifested by destructuring of the interlobular bile ducts, loss of their proper shape, expansion and unevenness of their lumens, deformation and thickening of the interstitial walls in 2-3 times, disorganization of cholangiocytes, thinning of the cell layer due to detachment of cholangiocytes, polymorphism of their nuclei, stratification, fragmentation of the lamina propria of the interlobular bile ducts, periductal edema, dilatation of interlobular portal tracts, "varicose" veins of the interlobular portal tracts, pronounced smooth muscle hyperplasia of the interlobular arteries, the presence of perivascular lymphocytic infiltrates. The data of the study can be used in practical medicine in the diagnosis and treatment of pathology of the bile ducts due to long-term use of opioids.


[1] Al-Nowfal, A., & Al-Abed, Y. A. (2016). Chronic biliary colic associated with ketamine abuse. International medical case reports journal, 9, 135-137. doi: 10.2147/IMCRJ.S100648
[2] Baumeister, D., Tojo, L. M., & Tracy, D. K. (2015). Legal highs: staying on top of the flood of novel psychoactive substances. Therapeutic advances in psychopharmacology, 5(2), 97-132. doi: 10.1177/2045125314559539
[3] Bulhakov, S. A. (2015). Opiate receptor agonists in gastroenterological practice. Evidence-Based Gastroenterology, 4(1), 14-18.
[4] De Angelis, C., Marietti, M., Bruno, M., Pellicano, R., & Rizzetto, M. (2015). Endoscopic ultrasound in common bile duct dilatation with normal liver enzymes. World journal of gastrointestinal endoscopy, 7(8), 799-805. doi: 10.4253/wjge.v7.i8.799
[5] Drahulian, M. V., Hulko, T. P., Kordium, V. A., Bubnov, R. V., & Deriabina, O. G. (2014). Simulation of toxic liver damage in a mouse line ICR. ScienceRise, 4(1(4)), 13-20.
[6] Farnia, M. R., Babaei, R., Shirani, F., Momeni, M., Hajimaghsoudi, M., Vahidi, E., & Saeedi, M. (2016). Analgesic effect of paracetamol combined with low-dose morphine versus morphine alone on patients with biliary colic: A double blind, randomized controlled trial. World journal of emergency medicine, 7(1), 25-29. doi: 10.5847/wjem.j.1920-8642.2016.01.004
[7] Fenner, E. K., Boguniewicz, J., Tucker, R. M., Sokol, R. J., & Mack, C. L. (2014). High-dose IgG therapy mitigates bile duct–targeted inflammation and obstruction in a mouse model of biliary atresia. Pediatric research, 76(1), 72-80. doi: 10.1038/pr.2014.46
[8] Fickert, P., Pollheimer, M. J., Beuers, U., Lackner, C., Hirschfield, G., Housset, C., ... & Melum, E. (2014). Characterization of animal models for primary sclerosing cholangitis (PSC). Journal of hepatology, 60(6), 1290-1303. doi: 10.1016/j.jhep.2014.02.006
[9] Franchitto, A., Onori, P., Renzi, A., Carpino, G., Mancinelli, R., Alvaro, D., & Gaudio, E. (2013). Recent advances on the mechanisms regulating cholangiocyte proliferation and the significance of the neuroendocrine regulation of cholangiocyte pathophysiology. Annals of translational medicine, 1(3), 27. doi: 10.3978/j.issn.2305-5839.2012.10.03
[10] Giusto, M., Barberi, L., Di Sario, F., Rizzuto, E., Nicoletti, C., Ascenzi, F., ... & Musarò, A. (2017). Skeletal muscle myopenia in mice model of bile duct ligation and carbon tetrachloride‐induced liver cirrhosis. Physiological reports, 5(7), e13153. doi: 10.14814/phy2.13153
[11] Hatano, R., Akiyama, K., Tamura, A., Hosogi, S., Marunaka, Y., Caplan, M. J., ... & Asano, S. (2015). Knockdown of ezrin causes intrahepatic cholestasis by the dysregulation of bile fluidity in the bile duct epithelium in mice. Hepatology, 61(5), 1660-1671. doi: 10.1002/hep.27565
[12] Hresko, N. I. (2016). Structural reorganization of the colon wall under the influence of external and internal factors. Bulletin of problems of biology and medicine, 2(2), 58-61.
[13] Hrytsko, R. Yu., Zadorozhnyi, A. M., Herasun, O. B., Piniazhko, O. R., Ivankiv, O. L., Orfin, A. Ya., ... & Myronenko, S. I. (2014). Hepatotoxicity of drugs. Hepatology, (2), 17-28.
[14] Huberhrits, N. B., Fomenko, P. G., Holubova, O. O., & Bieliaieva, N. V. (2016). Rational choice of proton pump inhibitor for the treatment of chronic pancreatitis in combination with drug-induced liver damage. Part 1. Baseline of the pancreas and liver, metabolic homeostasis. Quality of life of patients with combined pathology. Modern gastroenterology, (1), 63-81.
[15] Kartifuzova, Zh. V., Reshetnik, Ye. M., Bondzyk, O. V., Veselskyi, S. P., & Makarchuk, M. Yu. (2008). Effect of opioid peptides on cholera in rats with subacute alcoholic liver disease. Physics of the living, 16(1), 120-127.
[16] Kartifuzova, Zh. V., Reshetnik, Ye. M., Pustovalov, A. S., Dolhova, O. M., & Makarchuk, M. Yu. (2009). Influence of enkephalins under conditions of subacute alcoholic liver disease on morphometric parameters of its tissue and on the activity of serum enzymes. Achievements of clinical and experimental medicine, (2), 58-61.
[17] Kim, H. Y., Yang, H. K., Kim, S. H., & Park, J. H. (2014). Ibuprofen associated acute vanishing bile duct syndrome and toxic epidermal necrolysis in an infant. Yonsei medical journal, 55(3), 834-837. doi: 10.3349/ymj.2014.55.3.834
[18] Lohash, M. V. (2016). Pathomorphological changes of rat liver under the influence of opioid at the microstructural level. Bulletin of problems of biology and medicine, 2(2), 177-184.
[19] Miethke, A. G., Zhang, W., Simmons, J., Taylor, A., Shi, T., Shanmukhappa, S. K., ... & Nkinin, S. (2016). Pharmacological inhibition of ASBT changes bile composition and blocks progression of sclerosing cholangitis in mdr2 knockout mice. Hepatology (Baltimore, Md.), 63(2), 512-523. doi: 10.1002/hep.27973
[20] Patent, Ukraine (2012). № 76564U Method for modeling physical opioid dependence in rats. Onysko P. M., Paltov E. V., Fik V. B., Vilkhova I. V., Kryvko Yu. Ya., Yakymiv N. Ya., Fitkalo O. S., publ. 1.
[21] Pidvalna, U., Kost, A., & Mateshuk-Vatseba, L. (2018). Effect of Narcotic Analgesics on the Ultrastructure of the Eyeball (Experimental Study). Journal of Morphological Sciences, 35(04), 251-254. http://dx.doi.org/10.1055/s-0038-1676543
[22] Sheen, J. M., Chen, Y. C., Tain, Y. L., & Huang, L. T. (2014). Increased circulatory asymmetric dimethylarginine and multiple organ failure: bile duct ligation in rat as a model. International journal of molecular sciences, 15(3), 3989-4006. doi: 10.3390/ijms15033989
[23] Soleimanpour, H., Safari, S., Nia, K. S., Sanaie, S., & Alavian, S. M. (2016). Opioid drugs in patients with liver disease: a systematic review. Hepatitis monthly, 16(4), e32636. doi: 10.5812/hepatmon.32636
[24] Sundaram, V., & Björnsson, E. S. (2017). Drug‐induced cholestasis. Hepatology communications, 1(8), 726-735. doi: 10.1002/hep4.1088
[25] Tkach, S. M. (2015). Modern approaches to the treatment of pain of biliary and pancreatic genesis. News of medicine and pharmacy, (Gastr_4), 11-17.
[26] Vartak, N., Damle‐Vartak, A., Richter, B., Dirsch, O., Dahmen, U., Hammad, S., & Hengstler, J. G. (2016). Cholestasis‐induced adaptive remodeling of interlobular bile ducts. Hepatology, 63(3), 951-964. doi: 10.1002/hep.28373
[27] Zhang, Z., Li, Z., Zou, C., Zhang, J., Zhu, Y., & Miao, Y. (2015). Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis. International journal of clinical and experimental medicine, 8(8), 12086-12095. PMID: 26550120
[28] Zhuravlova, L. V., & Shekhovtsova, Yu. O. (2018). Drug-induced liver damage: tactics of diagnosis and treatment. Modern gastroenterology, 1(99), 47-52.
How to Cite
Mateshuk-Vatseba, L. R., & Hirniak, I. I. (2020). Features of the structural organization of the interlobular bile ducts under conditions of prolonged exposure to opioids in the experiment. Biomedical and Biosocial Anthropology, (36), 11-15. https://doi.org/10.31393/bba36-2019-02