MICROSCOPIC ARCHITECTURE OF THE LIVER OF EXPERIMENTAL RATS AFTER CANNABIDIOL OIL APPLICATIONS
Keywords:
experimental research, cannabidiol oil, liver vessels, histology, morphometric studies.
Abstract
Cannabidiol (CBD), found in Cannabis sativa (hemp), is a non-psychoactive phytochemical substance that has gained considerable popularity over the past decade. Cannabidiol is the main phytocannabinoid, its share in the plant extract can reach 40%. The aim of the study was to study and compare the microscopic architecture of the liver in normal and after 2 weeks cannabidiol oil applications in experimental rats. We conducted an experimental study of the effect of CBD on the liver 2 weeks after its use as a dietary supplement. The main group consisted of 18 rats to which 5 drops (3 mg 10%) of cannabidiol oil were added to the main feed once a day for 2 weeks. The control group consisted of 6 sexually mature white male rats, which were provided with water and food without any restrictions. Our research results showed that the use of CBD oil as a food supplement did not have a toxic effect on the liver, did not cause any damage.
References
1. Bhunchet, E., Wake, K. (1998). The portal lobule in rat liver fibrosis: a re-evaluation of the liver unit. Hepatology. 27(2):481–7. doi: 10.1002/hep.510270223.
2. Boggs, Douglas L., Nguyen, Jacques D., Morgenson, Daralyn., Taffe, Michael A., Ranganathan, Mohini. (2018). Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol. Neuropsychopharmacology. 43 (1):142–154. doi:10.1038/npp.2017.209
3. Breijyeh, Z., Jubeh, B., Bufo, SA., Karaman, R., Scrano L. (2021). Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses. Toxins (Basel). 13(2):117. doi: 10.3390/toxins13020117.
4. Bruni, C., Porter, K.R. (1965). The fine structure of the parenchymal cell of the normal rat liver. 1 General Observations. Am. J. Pathol. 46: 691.
5. Brunt, E.M., Gouw, A.S.H., Hubscher, S.G., Tiniakos, D.G., Bedossa, P., Burt, A.D., Callea, F., Clouston, A.D., Dienes, H.P., Goodman, Z.D., Roberts, E.A., Roskams, T., Terracciano, L., Torbenson, M.S. & Wanless, I.R. (2014) Pathology of the liver sinusoids. Histopathology 64 (7): 907–20.
6. Burkel, W.E. (1970). The fine structure of terminal branches of the hepatic arterial system of the rat. Anat. Rec. 167: 329.
7. Carvalho, R.K., Santos, M.L., Souza, M.R., Rocha, T.L., Guimaraes, F.S., Anselmo-Franci, J.A., Mazaro-Costa R. (2018). Chronic exposure to cannabidiol induces reproductive toxicity in male Swiss mice. J. Appl. Toxicol.; 38:1215–1223. doi: 10.1002/jat.3631.
8. Cassano, T., Villani, R., Pace, L., Carbone, A., Bukke, V.N., Orkisz, S. (2020). From Cannabis sativa to cannabidiol: promising therapeutic candidate for the treatment of neurodegenerative diseases. Front. Pharmacol. 11: 124. https://doi.org/10.3389/fphar.2020.00124.
9. Chevallier, M., Guerret, S., Chossegros, P., Gerard, F., Grimaud, J.A. (1994). A histological semiquantitative scoring system for evaluation of hepatic fibrosis in needle liver biopsy specimens: comparison with morphometric studies. Hepatology 20(2):349–55. PMID: 8045495.
10. Crawford, A.R., Lin, X-Z., Crawford, J.M. (1998). The normal adult human liver biopsy: a quantitative reference standard. Hepatology 28(2):323–31. doi: 10.1002/hep.510280206. PMID: 9695993.
11. Crippa, J.A., Hallak, J.E., Machado-de-Sousa, J.P., Queiroz, R.H., Bergamaschi, M., Chagas, M.H. (2013). Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report. J Clin Pharm Ther. 38:162–4. doi: 10.1111/jcpt.12018.
12. Devinsky, O., Cross, J.H., Wright, S. (2017). Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N. Eng. J. Med. 377:699–700. doi: 10.1056/NEJMoa1611618.
13. Elias, H., Popper, H. (1955). Venous distributions in livers. Comparison in man and experimental animals and applications to the morphogenesis of cirrhosis. AMA Arch Pathol. 59:332–40.
14. Fouad, A.A., Jresat, I. (2011). Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats. Eur. J. Pharmacol. 670:216–23. doi: 10.1016/j.ejphar.2011.08.048.
15. Gamble, L.J., Boesch, J.M., Frye, C.W., Schwark, W.S., Mann, S., Wolfe, L., Brown, H., Berthelsen, E.S., Wakshlag, J.J. (2018). Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs. Front. Vet. Sci. 5:165. doi: 10.3389/ fvets.2018.00165.
16. https://zakon.rada.gov.ua/laws/show/324-2021-п#Text
17. Jadoon, K.A., Tan, G.D., O’Sullivan, S.E. (2017). A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. JCI Insight. 2: e93760. doi: 10.1172/jci.insight.93760.
18. Kiernan, F. (1833). The anatomy and physiology of the liver. Philosophical Transactions of the Royal Society B: Biological Sciences, 123, 711–70.
19. Lamers, W. H., Vermeulen, J. L., Hakvoort, T. B., & Moorman, A. F. (1999). Expression pattern of glutamine synthetase marks transition from collecting into conducting hepatic veins. The Journal of Histochemistry and Cytochemistry, 47, 1507–12.
20. Lieber, C.S. (1982). Alcohol and the terminal hepatic venule. Gastroenterology 83:1158–1159.
21. Mak, K. M., & Png, C. Y. M. (2020). The hepatic central vein: Structure, fibrosis, and role in liver biology. The Anatomical Record, 303(7): 1747–67. doi: 10.1002/ar.24273. Epub 2019 Oct 18. PMID: 31581357.
22. Marx, T.K., Reddeman, R., Clewell, A.E., Endres, J.R., Beres, E., Vertesi, A., Glavits, R., Hirka, G., Szakonyine, I.P. (2018). An Assessment of the Genotoxicity and Subchronic Toxicity of a Supercritical Fluid Extract of the Aerial Parts of Hemp. J. Toxicol. 8143582. doi: 10.1155/2018/8143582.
23. Millar, S.A., Stone, N.L., Bellman, Z.D., Yates, A.S., England, T.J., O’Sullivan, S.E. (2019). A systematic review of cannabidiol dosing in clinical populations. Br. J. Clin. Pharmacol. 85: 1888–1900. https://doi.org/10.1111/bcp.14038.
24. Pacher, P., Kogan, N.M., Mechoulam, R., 2020. Beyond THC and endocannabinoids. Annu. Rev. Pharmacol. Toxicol. 60, 637–659. https://doi.org/10.1146/annurevpharmtox- 010818-021441.
25. Pertwee, R.G., Howlett, A.C., Abood, M.E., Alexander, S.P., Di Marzo, V., Elphick, M.R. (2010). International union of basic and clinical pharmacology. LXXIX.Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol. Rev. 62: 588–631. https://doi.org/10.1124/ pr.110.003004.
26. Pisanti, S., Malfitano, A.M., Ciaglia, E., Lamberti, A., Ranieri, R., Cuomo, G. (2017). Cannabidiol: state of the art and new challenges for therapeutic applications. Pharmacol. Ther. 175: 133–150. https://doi.org/10.1016/j.pharmthera.2017.02.041.
27. Porto, L.C., Chevallier, M., Grimaud, J.A. (1989). Morphometry of terminal hepatic veins. 1. Comparative study in man and baboon. Virchows Arch a Pathol Pathol Anat. 414:129–134.
28. Rappaport, A.M. (1966). The hepatic artery, its structural, circulatory, and metabolic fubctions. 3rd Int. Symp. Int. Assoc. Study of liver, Kyoto. T. Gastroent., p.116.
29. Rappaport, A.M. (1973). The microcirculatory hepatic unit. Microvasc. Res. 6: 212.
30. Rappaport, A.M. (1957). The structural and functional acinar unit of the liver; some histopathological considerations (Monograph). Int. Symp. Hepatitis Frontiers, Boston, Little, Brown.
31. Rezania, V., Coombe, D., & Tuszynski, J. A. (2016). A physiologically based flow network model for hepatic drug elimination III: 2D/3D DLA lobule models. Theoretical Biology & Medical Modelling, 13, 9–22.
32. Rosenkrantz, H., Fleischman, R.W., Grant, R.J. (1981). Toxicity of short-term administration of cannabinoids to rhesus monkeys. Toxicol. Appl. Pharmacol. 58:118–131. doi: 10.1016/0041-008X (81)90122-8.
33. Roskams, T., Desmet, V.J., Verslype, C. (2007). Development, structure, and function of the liver. In: Burt AD, Portmann BC, Ferrell LD, eds. MacSween’s Pathol ogy of the Liver. 5th ed. Edingurgh, UK: Churchill Livingstone/Elsevier. 1–74.
34. Ross, M.H., Pawlina, W. (2016). Digestive system III. Histology, a textbook, and atlas: with correlated cell and molecular biology. 7th ed. New York: Wolters Kluwer.
35. Ruijter, J.M., Gieling, R.G., Markman, M.M., Hagoort, J. and Lamers, W.H. (2004). Stereological measurement of porto-central gradients in gene expression in mouse liver. Hepatology, 39: 343-352. https://doi.org/10.1002/hep.20068
36. Saxena, R., Theise, N.D., Crawford, J.M. (1999). Microanatomy of the human liver–exploring the hidden interfaces. Hepatology. 30(6):1339–46. doi: 10.1002/hep.510300607. PMID: 10573509.
37. Schonhofen, P., de Medeiros, L.M., Bristot, I.J., Lopes, F.M., De Bastiani, M.A., Kapczinski, F., Crippa, J.A., Castro, M.A., Parsons, R.B., Klamt, F. (2015). Cannabidiol Exposure During Neuronal Differentiation Sensitizes Cells Against Redox-Active Neurotoxins. Mol. Neurobiol. 52:26–37. doi: 10.1007/s12035-014-8843-1.
38. Shevchuk, M.M. (2022). Macro- and microstructural liver arrangement in white rats in health. Bulletin of problems in biology and medicine. 3(166): 456-9 DOI:10.29254/2077-4214-2022-3- 166-456-459
39. Suriawinata AA, Thung SN. (2007). Liver. In: Mills SE, ed. Histology for Pathologists. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins. 685–703.
40. Thiele, E.A., Marsh, E.D., French, J.A., Mazurkiewicz-Beldzinska, M., Benbadis, S.R., Joshi, C., Lyons, P.D., Taylor, A., Roberts, C., Sommerville, K. (2018). Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 391:1085–1096. doi: 10.1016/ S0140-6736(18)30136-3.
41. Wagenaar, G. T., Moorman, A. F., Chamuleau, R. A., Deutz, N. E., De Gier, C., De Boer, P. A., Lamers, W. H. (1994). Vascular branching pattern and zonation of gene expression in the mammalian liver. A comparative study in rat, mouse, cynomolgus monkey, and pig. The Anatomical Record. 239: 441–52.
42. Wisse, E., Braet, F., Luo, D., De Zanger, R., Jans, D., Crabbe, E., Vermoesen, A. (1996). Structure and function of sinusoidal lining cells in the liver. Toxicol Pathol. 24(1):100–11. doi: 10.1177/019262339602400114. PMID: 8839287.
2. Boggs, Douglas L., Nguyen, Jacques D., Morgenson, Daralyn., Taffe, Michael A., Ranganathan, Mohini. (2018). Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol. Neuropsychopharmacology. 43 (1):142–154. doi:10.1038/npp.2017.209
3. Breijyeh, Z., Jubeh, B., Bufo, SA., Karaman, R., Scrano L. (2021). Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses. Toxins (Basel). 13(2):117. doi: 10.3390/toxins13020117.
4. Bruni, C., Porter, K.R. (1965). The fine structure of the parenchymal cell of the normal rat liver. 1 General Observations. Am. J. Pathol. 46: 691.
5. Brunt, E.M., Gouw, A.S.H., Hubscher, S.G., Tiniakos, D.G., Bedossa, P., Burt, A.D., Callea, F., Clouston, A.D., Dienes, H.P., Goodman, Z.D., Roberts, E.A., Roskams, T., Terracciano, L., Torbenson, M.S. & Wanless, I.R. (2014) Pathology of the liver sinusoids. Histopathology 64 (7): 907–20.
6. Burkel, W.E. (1970). The fine structure of terminal branches of the hepatic arterial system of the rat. Anat. Rec. 167: 329.
7. Carvalho, R.K., Santos, M.L., Souza, M.R., Rocha, T.L., Guimaraes, F.S., Anselmo-Franci, J.A., Mazaro-Costa R. (2018). Chronic exposure to cannabidiol induces reproductive toxicity in male Swiss mice. J. Appl. Toxicol.; 38:1215–1223. doi: 10.1002/jat.3631.
8. Cassano, T., Villani, R., Pace, L., Carbone, A., Bukke, V.N., Orkisz, S. (2020). From Cannabis sativa to cannabidiol: promising therapeutic candidate for the treatment of neurodegenerative diseases. Front. Pharmacol. 11: 124. https://doi.org/10.3389/fphar.2020.00124.
9. Chevallier, M., Guerret, S., Chossegros, P., Gerard, F., Grimaud, J.A. (1994). A histological semiquantitative scoring system for evaluation of hepatic fibrosis in needle liver biopsy specimens: comparison with morphometric studies. Hepatology 20(2):349–55. PMID: 8045495.
10. Crawford, A.R., Lin, X-Z., Crawford, J.M. (1998). The normal adult human liver biopsy: a quantitative reference standard. Hepatology 28(2):323–31. doi: 10.1002/hep.510280206. PMID: 9695993.
11. Crippa, J.A., Hallak, J.E., Machado-de-Sousa, J.P., Queiroz, R.H., Bergamaschi, M., Chagas, M.H. (2013). Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report. J Clin Pharm Ther. 38:162–4. doi: 10.1111/jcpt.12018.
12. Devinsky, O., Cross, J.H., Wright, S. (2017). Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N. Eng. J. Med. 377:699–700. doi: 10.1056/NEJMoa1611618.
13. Elias, H., Popper, H. (1955). Venous distributions in livers. Comparison in man and experimental animals and applications to the morphogenesis of cirrhosis. AMA Arch Pathol. 59:332–40.
14. Fouad, A.A., Jresat, I. (2011). Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats. Eur. J. Pharmacol. 670:216–23. doi: 10.1016/j.ejphar.2011.08.048.
15. Gamble, L.J., Boesch, J.M., Frye, C.W., Schwark, W.S., Mann, S., Wolfe, L., Brown, H., Berthelsen, E.S., Wakshlag, J.J. (2018). Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs. Front. Vet. Sci. 5:165. doi: 10.3389/ fvets.2018.00165.
16. https://zakon.rada.gov.ua/laws/show/324-2021-п#Text
17. Jadoon, K.A., Tan, G.D., O’Sullivan, S.E. (2017). A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. JCI Insight. 2: e93760. doi: 10.1172/jci.insight.93760.
18. Kiernan, F. (1833). The anatomy and physiology of the liver. Philosophical Transactions of the Royal Society B: Biological Sciences, 123, 711–70.
19. Lamers, W. H., Vermeulen, J. L., Hakvoort, T. B., & Moorman, A. F. (1999). Expression pattern of glutamine synthetase marks transition from collecting into conducting hepatic veins. The Journal of Histochemistry and Cytochemistry, 47, 1507–12.
20. Lieber, C.S. (1982). Alcohol and the terminal hepatic venule. Gastroenterology 83:1158–1159.
21. Mak, K. M., & Png, C. Y. M. (2020). The hepatic central vein: Structure, fibrosis, and role in liver biology. The Anatomical Record, 303(7): 1747–67. doi: 10.1002/ar.24273. Epub 2019 Oct 18. PMID: 31581357.
22. Marx, T.K., Reddeman, R., Clewell, A.E., Endres, J.R., Beres, E., Vertesi, A., Glavits, R., Hirka, G., Szakonyine, I.P. (2018). An Assessment of the Genotoxicity and Subchronic Toxicity of a Supercritical Fluid Extract of the Aerial Parts of Hemp. J. Toxicol. 8143582. doi: 10.1155/2018/8143582.
23. Millar, S.A., Stone, N.L., Bellman, Z.D., Yates, A.S., England, T.J., O’Sullivan, S.E. (2019). A systematic review of cannabidiol dosing in clinical populations. Br. J. Clin. Pharmacol. 85: 1888–1900. https://doi.org/10.1111/bcp.14038.
24. Pacher, P., Kogan, N.M., Mechoulam, R., 2020. Beyond THC and endocannabinoids. Annu. Rev. Pharmacol. Toxicol. 60, 637–659. https://doi.org/10.1146/annurevpharmtox- 010818-021441.
25. Pertwee, R.G., Howlett, A.C., Abood, M.E., Alexander, S.P., Di Marzo, V., Elphick, M.R. (2010). International union of basic and clinical pharmacology. LXXIX.Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol. Rev. 62: 588–631. https://doi.org/10.1124/ pr.110.003004.
26. Pisanti, S., Malfitano, A.M., Ciaglia, E., Lamberti, A., Ranieri, R., Cuomo, G. (2017). Cannabidiol: state of the art and new challenges for therapeutic applications. Pharmacol. Ther. 175: 133–150. https://doi.org/10.1016/j.pharmthera.2017.02.041.
27. Porto, L.C., Chevallier, M., Grimaud, J.A. (1989). Morphometry of terminal hepatic veins. 1. Comparative study in man and baboon. Virchows Arch a Pathol Pathol Anat. 414:129–134.
28. Rappaport, A.M. (1966). The hepatic artery, its structural, circulatory, and metabolic fubctions. 3rd Int. Symp. Int. Assoc. Study of liver, Kyoto. T. Gastroent., p.116.
29. Rappaport, A.M. (1973). The microcirculatory hepatic unit. Microvasc. Res. 6: 212.
30. Rappaport, A.M. (1957). The structural and functional acinar unit of the liver; some histopathological considerations (Monograph). Int. Symp. Hepatitis Frontiers, Boston, Little, Brown.
31. Rezania, V., Coombe, D., & Tuszynski, J. A. (2016). A physiologically based flow network model for hepatic drug elimination III: 2D/3D DLA lobule models. Theoretical Biology & Medical Modelling, 13, 9–22.
32. Rosenkrantz, H., Fleischman, R.W., Grant, R.J. (1981). Toxicity of short-term administration of cannabinoids to rhesus monkeys. Toxicol. Appl. Pharmacol. 58:118–131. doi: 10.1016/0041-008X (81)90122-8.
33. Roskams, T., Desmet, V.J., Verslype, C. (2007). Development, structure, and function of the liver. In: Burt AD, Portmann BC, Ferrell LD, eds. MacSween’s Pathol ogy of the Liver. 5th ed. Edingurgh, UK: Churchill Livingstone/Elsevier. 1–74.
34. Ross, M.H., Pawlina, W. (2016). Digestive system III. Histology, a textbook, and atlas: with correlated cell and molecular biology. 7th ed. New York: Wolters Kluwer.
35. Ruijter, J.M., Gieling, R.G., Markman, M.M., Hagoort, J. and Lamers, W.H. (2004). Stereological measurement of porto-central gradients in gene expression in mouse liver. Hepatology, 39: 343-352. https://doi.org/10.1002/hep.20068
36. Saxena, R., Theise, N.D., Crawford, J.M. (1999). Microanatomy of the human liver–exploring the hidden interfaces. Hepatology. 30(6):1339–46. doi: 10.1002/hep.510300607. PMID: 10573509.
37. Schonhofen, P., de Medeiros, L.M., Bristot, I.J., Lopes, F.M., De Bastiani, M.A., Kapczinski, F., Crippa, J.A., Castro, M.A., Parsons, R.B., Klamt, F. (2015). Cannabidiol Exposure During Neuronal Differentiation Sensitizes Cells Against Redox-Active Neurotoxins. Mol. Neurobiol. 52:26–37. doi: 10.1007/s12035-014-8843-1.
38. Shevchuk, M.M. (2022). Macro- and microstructural liver arrangement in white rats in health. Bulletin of problems in biology and medicine. 3(166): 456-9 DOI:10.29254/2077-4214-2022-3- 166-456-459
39. Suriawinata AA, Thung SN. (2007). Liver. In: Mills SE, ed. Histology for Pathologists. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins. 685–703.
40. Thiele, E.A., Marsh, E.D., French, J.A., Mazurkiewicz-Beldzinska, M., Benbadis, S.R., Joshi, C., Lyons, P.D., Taylor, A., Roberts, C., Sommerville, K. (2018). Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 391:1085–1096. doi: 10.1016/ S0140-6736(18)30136-3.
41. Wagenaar, G. T., Moorman, A. F., Chamuleau, R. A., Deutz, N. E., De Gier, C., De Boer, P. A., Lamers, W. H. (1994). Vascular branching pattern and zonation of gene expression in the mammalian liver. A comparative study in rat, mouse, cynomolgus monkey, and pig. The Anatomical Record. 239: 441–52.
42. Wisse, E., Braet, F., Luo, D., De Zanger, R., Jans, D., Crabbe, E., Vermoesen, A. (1996). Structure and function of sinusoidal lining cells in the liver. Toxicol Pathol. 24(1):100–11. doi: 10.1177/019262339602400114. PMID: 8839287.
Abstract views: 100 PDF Downloads: 63
Published
2023-09-01
How to Cite
Shevchuk, M., & Volos, L. (2023). MICROSCOPIC ARCHITECTURE OF THE LIVER OF EXPERIMENTAL RATS AFTER CANNABIDIOL OIL APPLICATIONS. Scientific Journal of Polonia University, 58(3), 320-332. https://doi.org/10.23856/5845
Section
HEALTH, ENVIRONMENT, DEVELOPMENT
