ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 8 of 57
Up
JMBS 2020, 5(1): 62–66
https://doi.org/10.26693/jmbs05.01.062
Experimental Medicine and Morphology

Ultrastructural Organization of the Cervix Muscular Layer in White Laboratory Rats under Long–Term Opioid Influence

Mateshuk-Vatseba L. R., Ivankiv Ya. T., Podolyuk M. V.
Abstract

The problem of drug addiction is a growing concern among specialists in various fields. Drug abuse provokes not only physical and mental addiction, but has also a negative effect on the physiological parameters of the body. The development of drug addiction in women is much faster than in men, and the significant structural, morphological and functional changes of the genital organs raise the burning issue of reproductive health worldwide. The considerable use of drugs in clinical practice without sufficient experimental research has necessitated a detailed study of the effect of opioids on the structural organization of organs. The purpose of the study was to establish and describe ultrastructural features of the cervix muscular layer in white lab rats within a norm and at the 2nd, 4th, and 6th weeks of nalbuphine exposure. Material and methods. The research was performed on 24 sexually mature white female rats 3.0–3.5 months old with the initial body weight of 160–180 g. The experimental animals were divided into 3 groups, each group of animals was administered intramuscularly nalbuphine daily during 2, 4, and 6 weeks. The control group included 9 female rats, which got injected with 0.9 % NaCl solution throughout the experiment. The research was performed with the help of electron microscopy. The sections were prepared on a UMTP–6M ultramicrotome using a diamond knife (DIATOM). The sections were examined with a TEM–100 transmission electron microscope. Photographs were taken with a digital camera SONY–H9. Results and discussion. Excessive and uncontrolled administration of opioids has a negative impact on the female body. Eriksson and Ray's research shows that morphine intake during pregnancy leads to delayed growth, weight loss, and early abortion. A number of studies have described the effects of various opioids on the myometrium of pregnant female rats, with impaired uterine muscle contractility. Maryam Dehghan et al in an experiment in mice showed that morphine causes deformation and destruction of the nuclear membrane of epithelial cells of the endometrium at the ultrastructural level, observed the distance between nuclei and heterochromatin, which was not observed in the control groups. Similar ultrastructural changes of muscle tissue were observed in the study of the effect of nalbuphine on cardiomyocytes, where an electron-microscopic examination revealed expansion of the intercellular space, destroyed mitochondria, mosaic damage of cardiomyocytes, chromatic dislocation. Conclusion. Chronic exposure to nalbuphine causes significant ultrastructural changes in the cervix. Even in the early stages of the experiment (2 weeks) it was possible to trace the disorders that were the consequences of the introduction of the opioid into the body of the experimental animal. Each subsequent phase of the experiment revealed deepening changes in the structure of the muscle cells. The resulting damage showed the ability of the long-term use of the opioid to cause irreversible changes in structure and function at all levels, starting from ultrastructural.

Keywords: nalbufin, electron microscopy, cervix, muscle layer

Full text: PDF (Ukr) 365K

References
  1. Bekesevych AM, Mateshuk-Vatseba LR, Oliynyk IYu, Zinko AV. Vplyv tryvalogo vvedennya opioyidu na ultrastrukturnu organizatsiyu biloyi rechovyny golovnogo mozku v eksperymenti [The Influence of Long-Term Opioid Administration on the Ultrastructural Organization of the White Substance of the Brain in the Experiment]. Ukrayinskyy zhurnal medytsyny, biologiyi ta sportu. 2018; 3(6): 31–5. [Ukrainian] https://doi.org/10.26693/jmbs03.06.031
  2. Pidvalna UYe. Strukturna organizatsiya organiv i system pid vplyvom opioyidiv [Structural organization of organs and systems under the influence of opioids]. Eksperymentalna ta klinichna fiziologiya i biokhimiya. 2014; 1: 71–8. [Ukrainian]
  3. Ivankiv YaT, Mateshuk-Vatseba LR. Morfologichni osoblyvosti matky v normi ta pry patologiyi [Morphological Features of Healthy and Pathological Uterus]. Ukrayinskyy zhurnal medytsyny, biologiyi ta sportu. 2018; 1(17): 21–8. [Ukrainian] https://doi.org/10.26693/jmbs04.01.021
  4. Smith CL, Severtsen B, Vandermause R, Barbosa-Leiker C, Wilson M, Roll J. Seeking Chronic Pain Relief: A Hermeneutic Exploration. Pain Management Nursing. 2018 Dec; 19(6): 652–62. PMID: 29935910. https://doi.org/10.1016/j.pmn.2018.05.001
  5. Isenberg SR, Maragh-Bass AC, Ridgeway K, Beach MC, Knowlton AR. A qualitative exploration of chronic pain and opioid treatment among HIV patients with drug use disorders. Journal of Opioid Management. 2017 Jan/Feb; 13(1): 5–16. PMID: 28345742. PMCID: PMC5560049. https://doi.org/10.5055/jom.2017.0363
  6. Organization WH. Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. New York: World Health Organization; 2009. Available from: https://www.who.int/substance_abuse/publications/opioid_dependence_guidelines.pdf
  7. World Drug Report 2018 (United Nations publication, Sales No.E.18.XI.9) [Internet]. 2018. Available from: https://www.unodc.org/wdr2018/
  8. Gartry CC, Oviedo-Joekes E, Laliberté N, Schechter MT. The trials and tribulations of implementing a heroin assisted treatment study in North America. Harm Reduction J. 2009 Jan 21; 6: 2. PMID: 19159475. PMCID: PMC2639576. https://doi.org/10.1186/1477–7517–6–2
  9. Vucinovic M, Roje D, Vucinovic Z, Capkun V, Bucat M, Banovic I. Maternal and Neonatal Effects of Substance Abuse during Pregnancy: Our Ten–year Experience. J Yonsei Med. 2008; 49: 705–13. PMID: 18972589. PMCID: PMC2615365. https://doi.org/10.3349/ymj.2008.49.5.705
  10. Patent 76564 U Ukraine, MPK A 61 K 31/00. Sposib modelyuvannya fizychnoyi opioyidnoyi zalezhnosti u shchuriv [Method for modeling physical opioid dependence in rats] / Onysko RM, Paltov YeV, Fik VB, Vilkhova IV, Kryvko YuYa, Yakymiv NYa, Fitkalo OS (UA); zayavnik i vlasnik patentu Lvivskyy natsionalnyy medychnyy universytet imeni Danyla Galytskogo (UA). № U201207124; zayavl 12.06.2012; opubl 10.01.2013. Byul № 1. [Ukrainian]
  11. Eriksson PS, Ronnback L. Effect of prenatal morphine treatment of rats on mortality, body weight and analgesic response in the offspring. Drug Alcohol Depend 1989; 24: 187–94. https://doi.org/10.1016/0376–8716(89)90055–0
  12. Ray JR, Dubinj W, Blechner JN. Fetal growth retardation fallowing matenal morphine administration. Biol Neonal. 1977; 32: 222–8. PMID: 603807. https://doi.org/10.1159/000241021
  13. Kayacan N, Ertugrul F, Arici G, Kkar M, Erman M. in vitro effect of opioids on pregnant uterine muscle. Adv Ther. 2007; 24: 368–75. PMID: 17565928. https://doi.org/10.1007/BF02849906
  14. Yoo KY, Lee J, Kim HS, Jeong SW. The effects of opioids on isolated human pregnant uterine muscles. Anesth Analg. 2001; 92: 1006–9. PMID: 11273940. https://doi.org/10.1097/00000539–200104000–00037
  15. Dehghan M, Jafarpour M, Mahmoudian Al. The effect of morphine administration on structure and ultrastructure of uterus in pregnant mice. Iranian Journal of Reproductive Medicine. 2010; 8(3): 111–8.
  16. Pokotylo VYu. Ultrastrukturni osoblyvosti miokarda shchura ta yogo gemomikrotsyrkulyatornogo rusla na rannikh terminakh perebigu opioyidnoyi intoksykatsiyi [Ultrastructural features of rat myocardium and its hemomicrocirculatory bed at the early stages of opioid intoxication]. Visnyk problem biologiyi i medytsyny. 2017; 1(135): 304–9. [Ukrainian]
  17. Radulovic NV, Ekerhovd E, Abrahamsson G, Norstrom A. Cervical priming in the first trimester: morphological and biochemical effects of misoprostol and isosorbide mononitrate. Acta Obstet Gynecol Scand. 2009; 88: 43–51. PMID: 19034732. https://doi.org/10.1080/00016340802585440