CK19 and OV6 Expressions in the Liver of 2-AAF/CCl4 Rat Model

Authors

  • Romy Arwinda Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Master’s Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Isabella Kurnia Liem Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Integrated Laboratory, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Ayu Eka Fatril Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Fanny Oktorina Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Firda Asma'ul Husna Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Ria Kodariah Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Puspita Eka Wuyung Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Animal Research Facilities, Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.7923

Keywords:

Rat model, Liver injury, 2-AAF/CCl4 OV6, CK19

Abstract

BACKGROUND: Liver regeneration on a chronic liver injury with rat model research is urgent to study the pathology of human chronic diseases. 2-Acetylaminofluorene (2-AAF) and Carbon Tetrachloride (CCl4) can be applied to study about liver regeneration by liver stem cells, known as oval cells. The use of 2-AAF and CCl4 (2-AAF/CCl4) to induce chronic liver injury can lead severe hepatocyte damages and extensive fibrosis.

AIM: to observed the OV6 and CK19 expression in the liver of 2AAF/CCl4 rat model.

METHODS: In this research, a high dose of 2-AAF (10mg/kg) was applied and combined repeatedly with CCl4 (2ml/kg) for 12 weeks. An immunohistochemistry (IHC) procedure by using OV6 and CK19 antibodies was also applied to examine the regeneration of oval cells. Both antibodies expressions were then examined semi-quantitatively according to the expressions percentage of each sample based on the liver zone. We have observed the OV6 and CK19 expressions in every zone, including in portae hepatis area.  

RESULTS: The results showed that OV6 and CK19 with the highest expression in the zone I. A significant difference between OV6 and CK19 expressions was revealed in healthy (control group) and 2-AAF/CCl4 groups (both indicating p=0.045). Moreover, a ductular reaction was also found in Zone I and II of the 2-AAF/CCl4.

CONCLUSIONS: We conclude that 2-AAF/CCl4 induced chronic rat liver injury model, could be utilized to investigate the oval cells with OV6 and CK19 expression.

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References

Liem IK, Zakiyah Z, Oktavina R, Deraya IE, Kodariah R, Krisnuhoni E, et al. Comparison of two methods of 2AFF/CCl4 exposure to induce severe liver injury. Elektron J Kedokt Indones. 2020;8(3):164-71. https://doi.org/10.23886/ejki.8.12368 DOI: https://doi.org/10.23886/ejki.8.12368.

Pinzani M. Pathophysiology of liver fibrosis. Dig Dis. 2015;33(4):492-7. https://doi.org/10.1159/000374096 PMid:26159264 DOI: https://doi.org/10.1159/000374096

Povero D, Busletta C, Novo E, di Bonzo LV, Cannito S, Paternostro C, et al. Liver fibrosis: A dynamic and potentially reversible process. Histol Histopathol. 2010;25(8):1075-91. https://doi.org/10.14670/HH-25.1075 PMid:20552556

Tsochatzis EA, Bosch J, Burroughts AK. Liver cirrhosis. Lancet. 2014;383(9930):1749-61. https://doi.org/10.1016/ S0140-6736(14)60121-5 PMid:24480518 DOI: https://doi.org/10.1016/S0140-6736(14)60121-5

Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology. 2008;134(6):1655-69. https://doi.org/10.1053/j.gastro.2008.03.003 PMid:18471545 DOI: https://doi.org/10.1053/j.gastro.2008.03.003

Zhuo JY, Lu D, Tan WY, Zheng SS, Shen YQ, Xu X. CK19- positive hepatocellular carcinoma is a characteristic subtype. J Cancer. 2020;11(17):5069-77. https://doi.org/10.7150/jca.44697 PMid:32742454 DOI: https://doi.org/10.7150/jca.44697

Roskams T, de Vos R, van Eyken P, Myazaki H, van Damme B, Desmet V. Hepatic OV-6 expression in human liver disease and rat experiments: Evidence for hepatic progenitor cells in man. J Hepatol. 1998;29(3):455-63. https://doi.org/10.1016/s0168-8278(98)80065-2 PMid:9764994 DOI: https://doi.org/10.1016/S0168-8278(98)80065-2

Katoonizadeh A, Poustchi H, Malekzadeh R. Hepatic progenitor cells in liver regeneration: Current advances and clinical perspectives. Liver Int. 2014;1-9. https://doi.org/10.1111/liv.12573 PMid:24750779 DOI: https://doi.org/10.1111/liv.12573

Michalopoulos GK, DeFrances MC. Liver regeneration. Science. 1997;276:60-6. https://doi.org/10.1126/science.276.5309.60 PMid:9082986 DOI: https://doi.org/10.1126/science.276.5309.60

Fausto N, Campbell JS, Riehle KJ. Liver regeneration. Hepatology. 2006;43 Suppl 2:S45-53. https://doi.org/10.1002/hep.20969 PMid:16447274 DOI: https://doi.org/10.1002/hep.20969

Fausto N, Campbell JS. The role of hepatocytes and oval cells in liver regeneration and repopulation. Mech Dev. 2003;120(1):117-30. https://doi.org/10.1016/s0925-4773(02)00338-6 PMid:12490302 DOI: https://doi.org/10.1016/S0925-4773(02)00338-6

Dusabineza AC, van Hul NK, Abarca-Quinones J, Starkel P, Najimi M, Leclercq IA. Participation of liver progenitor cells in liver regeneration: Lack of evidence in the AAF/PH rat model. Lab Invest. 2012;92(1):72-81. https://doi.org/10.1038/labinvest.2011.136 PMid:21912377 DOI: https://doi.org/10.1038/labinvest.2011.136

Berumen J, Baglieri J, Kisseleva T, Mekeel K. Liver fibrosis: Pathophysiology and clinical implications. WIREs Mech Dis. 2021;13(1):e1499.https://doi.org/10.1002/wsbm.1499 DOI: https://doi.org/10.1002/wsbm.1499

Yin C, Evason KJ, Asahina K, Stainier DY. Hepatic stellate cells in liver development, regeneration, and cancer. J Clin Invest. 2013;123(5):1902-10. https//doi/org/10.1172/JCI66369 PMid:23635788 DOI: https://doi.org/10.1172/JCI66369

Yanger K, Knigin D, Zong Y, Maggs L, Gu G, Akiyama H, et al. Adult hepatocytes are generated by self-duplication rather than stem cell differentiation. Cell Stem Cell. 2014;15:340-9. https://doi.org/10.1016/j.stem.2014.06.003 PMid:25130492 DOI: https://doi.org/10.1016/j.stem.2014.06.003

Bagnyukova TV, Tryndyak VP, Montgomery B, Churchwell MI, Karpf AR, James SR, et al. Genetic and epigenetic changes in rat preneoplastic liver tissue induced by 2-acetylaminofluorene. Carcinogenesis. 2008;3(29):638-46. https://doi.org/0.1093/carcin/bgm303 PMid:18204080 DOI: https://doi.org/10.1093/carcin/bgm303

Goradel NH, Darabi M, Shamsasenjan K, Ejtehadifar M, Zahedi S. Methods of liver stem cell therapy in rodents as models of human liver regeneration in hepatic failure. Tabriz Univ Med Sci. 2015;5(3):293-8. https://doi.org/10.5681/apb.2015.041 PMid:26504749 DOI: https://doi.org/10.15171/apb.2015.041

Abdellatif H, Shiha G, Saleh DM, Eltahry H, Botros KG. Effect of human umbilical cord blood stem cell transplantation on oval cell response in 2-AAF/CCL4 liver injury model: Experimental immunohistochemical study. Inflamm Regen. 2017;37:5. https:// doi.org/10.1186/s41232-017-0035-8 PMid:29259704 DOI: https://doi.org/10.1186/s41232-017-0035-8

Chen J, Zhang X, Xu Y, Li X, Ren S, Zhou Y, et al. Hepatic progenitor cells contribute to the progression of 2-acetylaminofluorene/ carbon tetrachloride-induced cirrhosis via the non-canonical Wnt pathway. PLoS One. 2015;10(6):e0130310. https://doi.org/10.1371/journal.pone.0130310 PMid:26087010 DOI: https://doi.org/10.1371/journal.pone.0130310

Michalopoulos GK, Bhushan B. Liver regeneration: Biological and pathological mechanisms and implications. Nat Rev Gastroenterol Hepatol. 2021;18(1):40-55. https://doi.org/10.1038/s41575-020-0342-4 PMid:32764740 DOI: https://doi.org/10.1038/s41575-020-0342-4

Itoh T, Miyajima A. Liver regeneration by stem/progenitor cells. Hepatology. 2014;59(4):1617-26. https://doi.org/10.1002/hep.26753 PMid:24115180 DOI: https://doi.org/10.1002/hep.26753

Tanimizu N, Tsujimura T, Takahide K, Kodama T, Nakamura K, Miyajima A. Expression of Dlk/Pref-1 defines a subpopulation in the oval cell compartment of rat liver. Gene Expr Patterns. 2004;5(2):209-18. https://doi.org/10.1016/j.modgep.2004.08.003 PMid:15567716 DOI: https://doi.org/10.1016/j.modgep.2004.08.003

Hasan SK, Sultana S. Geraniol attenuates 2-acetylaminofluorene induced oxidative stress, inflammation and apoptosis in the liver of Wistar rats. Toxicol Mech Methods. 2015;25(7):559-73. https://doi.org/10.3109/15376516.2015.1070225 PMid:26364502

Liem IK, Oktavina R, Zakiyah, Anggraini D, Deraya IE, Kodariah R, et al. Intravenous injection of umbilical cord-derived mesenchymal stem cells improved regeneration of rat liver after 2AAF/CCl4-induced injury. Online J Biol Sci. 2021;21(2):317-26. https://doi.org/10.3844/ojbsci.2021.317.326 DOI: https://doi.org/10.3844/ojbsci.2021.317.326

Johnston DE, Kroening C. Mechanism of early carbon tetrachloride toxicity in cultured rat hepatocytes. Pharmacol Toxicol. 1998;83(6):231-9. https://doi.org/10.1111/j.1600-0773.1998.tb01475.x PMid:9868740 DOI: https://doi.org/10.1111/j.1600-0773.1998.tb01475.x

Liu D, Yovchev MI, Zhang J, Alfieri AA, Tchaikovskaya T, Laconi E, et al. Identification and characterization of mesenchymal-epithelial progenitor-like cells in normal and injured rat liver. Am J Pathol. 2015;185(1):110-28. https://doi.org/10.1016/j.ajpath.2014.08.029 PMid:25447047 DOI: https://doi.org/10.1016/j.ajpath.2014.08.029

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Published

2022-01-30

How to Cite

1.
Arwinda R, Liem IK, Fatril AE, Oktorina F, Husna FA, Kodariah R, Wuyung PE. CK19 and OV6 Expressions in the Liver of 2-AAF/CCl4 Rat Model. Open Access Maced J Med Sci [Internet]. 2022 Jan. 30 [cited 2024 Apr. 26];10(A):340-5. Available from: https://oamjms.eu/index.php/mjms/article/view/7923