Correlation between Kupffer Cell Infiltration and Liver Parenchymal Cell Damages in Immunosuppressed Drugs-Induced Rats

Agni Febrina Pargaputri, Endah Wahjuningsih, Dwi Andriani

Abstract


The liver is the largest organ in the body, composed of both parenchymal and non-parenchymal cells. Chemical substances and various drugs can induce liver injury and involve Kupffer cells which are non-parenchymal cells that release biologically active substances, promoting pathological processes. This study aimed to evaluate the correlation between the number of Kupffer cells and liver parenchymal cell damages in immunosuppressed, drug-induced rats. The study was conducted from July to December 2019 at the Oral Biology Laboratory of the Faculty of Dentistry and the Biochemical Laboratory of the Faculty of Medicine at Universitas Hang Tuah Surabaya. Twelve healthy male Wistar rats were divided into two groups: Healthy (H) and Immunosuppressed Drug-Induced (ID) groups. Immunosuppression was induced using dexamethasone (0.5 mg/day/rat), administered orally for 14 days, combined with tetracycline (1%/day/rat). Liver samples from all rats were examined for Kupffer cell count and parenchymal cell damages were assessed using a light microscope with 400x magnification. Results revealed a significant difference in the number of Kupffer cells and liver parenchymal cell damages between the H and ID groups (p<0.05). Pearson correlation analysis indicated a significant correlation between Kupffer cell number and parenchymal cell damages (p=0.000). Continuous administration of immunosuppressive drugs may activate Kupffer cells, leading to damage of liver parenchymal cells. In conclusion, the infiltration of Kupffer cells is associated with liver parenchymal cell damages, mediated by various factors in the immunosuppressed drug-induced rat model.


Keywords


Immunosuppressed drugs, Kupffer cell, liver parenchymal cell

Full Text:

PDF

References


  1. Guyton and Hall. Textbook of medical physiology. 14th ed. Singapore: Elsevier; 2021. p. 871.
  2. Mohammed K. Hassani. Liver structure, function and its interrelationships with other organs: a review. International Journal Dental and Medical Sciences Research. 2022;4(1):88–92. doi: 10.35629/5252-04018892
  3. Pargaputri AF, Andriani D, Hartono MR, Widowati K. Effect of hyperbaric oxygen treatment on liver hepatocyte damage in oral candidiasis immunosuppressed rats. Odonto: Dental Journal. 2022;9(2):319–26. doi: 10.30659/odj.9.2.319-326
  4. Yaseen H, Haroon K. Immunosuppressive drugs. Encyclopedia of Infection and Immunity. 2022:726–40. doi: 10.1016/B978-0-12-818731-9.00068-9
  5. Fenella BP, Thura WH, Mina K, Phyo KM. Systematic review of immunosuppressant guidelines in the COVID-19 pandemic. Ther Adv Drug Saf. 2021;12:2042098620985687. doi: 10.1177/2042098620985687
  6. Elena T, Judit C, Mercedes R, MA Isabel Lucena, Raúl JA. Hepatotoxicity induced by new immunosuppressants. Gastroenterol Hepatol. 2010;33(1):54–65. doi: 10.1016/j.gastrohep.2009.07.003.
  7. Hiroko T, Shuhei N. Importance of kupffer cells in the development of acute liver injuries in mice. Int. J. Mol. Sci. 2014;15:7711–30. doi:10.3390/ijms15057711
  8. Prasetiawan E, Sabri E, Ilyas S. Gambaran histologis hepar mencit (mus musculus l.) strain ddw setelah pemberian ekstrak n-heksan buah andaliman (Zanthoxylum acanthopodium Dc.) selama masa pra implantasi dan pasca implantasi. Saintia Biol. 2012;1(1):40–5.
  9. Pargaputri AF, Andriani D. Serum albumin levels of oral candidiasis immunosuppressed rats treated with hyperbaric oxygen. International Journal of Integrated Health Sciences. 2020;8(1):8–13. doi: 10.15850/ijihs.v8n1.2086
  10. Pargaputri AF, Andriani D. Hepatocellular liver function of immunosuppressed rats with oral candidiasis after hyperbaric oxygen treatment: Alanine transaminase and aspartate transaminase levels. Arch Orofac Sci. 2021;16(Supp.1):5–9. doi: 10.21315/aos2021.16.s1.2
  11. Oliver K, Frank T. Liver macrophages in tissue homeostasis and disease. Nature Reviews Immunology. 2017;17:306–21. doi: 10.1038/nri.2017.11
  12. Meurman JH, Siikala E, Richardson M, Rautemaa R. Non-Candida albicans Candida yeasts of the oral cavity. In: Méndez-Vilas A (ed.), Communicating Current Research and Educational Topics and Trends in Applied Microbiology. 2017:719–31.
  13. Ruth AR, Patricia EG, Cynthia J, Lisa MK, Ivan R, James EK. Role of the Kupffer cell in mediating hepatic toxicity and carcinogenesis. Toxicol Sci. 2007;96(1): 2–15. doi: 10.1093/toxsci/kfl173.
  14. Elise Slevin, Leonardo Baiocchi, Nan Wu, Burcin Ekser, Keisaku Sato, Emily Lin, et al. Kupffer cells: inflammation pathways and cell-cell interactions in alcohol-associated liver disease. Am J Pathol. 2020;190(11):2185–93. doi: 10.1016/j.ajpath.2020.08.014.
  15. Subhra KB and Alberto M. Kupffer Cells in Health and Disease. Macrophages: biology and role in the pathology of diseases. 2014:217–47.
  16. M. Teresa Donato, Gloria Gallego-Ferrer, and Laia Tolosa. In vitro models for studying chronic drug-induced liver injury. Int. J. Mol. Sci. 2022;23(19):11428. doi: 10.3390/ijms231911428
  17. Pargaputri AF, Andriani D. The effect of hyperbaric oxygen therapy to the amount of lymphocytes in oral candidiasis immunosuppressed model. Denta J Kedokt Gigi. 2018;12(2):36–44.
  18. Andriani D, Pargaputri AF. Enhance of il-22 expression in oral candidasis immunosuppressed model with acanthus ilicifolius extract therapy. IOP Conf Ser Earth Environ Sci. 2019;217:012056.
  19. Paramita DO, Endah W, Dwi A. Efektivitas suplementasi teripang emas (Stichopus hermanii) dalam mencegah terjadinya oral candidiasis pada tikus wistar. Denta 2018; 12(1):9–15. doi: 10.30649/denta.v12i1.155
  20. Hajira Basit, Michael L. Tan, Daniel R. Webster. Histology, kupffer cell. Treasure Island (FL): StatPearls Publishing; 2022.
  21. David BA, Rezende RM, Antunes MM, Santos MM, Freitas LM, Diniz AB, et al. Combination of mass cytometry and imaging analysis revealsorigin, location, and functional repopulation of liver myeloid cells in mice. Gastroenterology. 2016;151:1176–91. doi: 10.1053/j.gastro.2016.08.02415.
  22. Kopec AK, Joshi N, Cline-Fedewa H, Wojcicki AV, Ray JL, Sullivan BP, et al. Fibrinogen drives repair after acetaminophen-induced liver injury via leukocyte alphambeta2 integrin-dependent upregulation of mmp12. J Hepatol. 2017;66:787–97. doi: https://doi.org/10.1053/j.gastro.2016.08.024.
  23. Li W, Chang N, Li L. Heterogeneity and function of kupffer cells in liver injury. Front. Immunol. 2022;13:940867. doi: 10.3389/fimmu.2022.940867
  24. Farah Tasnim, Xiaozhong Huang, Christopher ZWL, Florent Ginhoux, and Hanry Yu. Recent advances in models of immune-mediated drug-induced liver injury. Front. Toxicol. 3: 605392. doi: 10.3389/ftox.2021.605392
  25. Takashi Sakai and Wen-Ling Lin. Kupffer cells as a target for immunotherapy. sakai t, lin w-l. kupffer cells as a target for immunotherapy. J Multidisciplinary Scientific Journal. 2022;5:532–7. doi: 10.3390/j5040036
  26. Laura JD, Mark B, Hui T, Michele TP, Laura EN. Kupffer cells in the liver. Compr Physiol. 2013;3(2):785–97. doi: 10.1002/cphy.c120026
  27. Mark B, Laura JD, Zhang-Xu L, Hui T, Laura EN. Macrophages and kupffer cells in drug-induced liver injury. Drug-Induced Liver Disease (Third Edition). 2013. Academic press. p: 147-155. doi: 10.1016/B978-0-12-387817-5.00009-1
  28. Reham Hassan. Kupffer cells in hepatotoxicity. EXCLI Journal. 2020;19:1156-1157.
  29. Kendran AAS, Arjana AA, Pradnyantar AASI. Aktivitas enzim alanine-aminotransferase dan aspartate aminotransferase pada tikus putih jantan yang diberi ekstrak buah pinang. Buletin Veteriner Udayana. 2017;9(2):132–8.




DOI: https://doi.org/10.15395/mkb.v56.3569

Article Metrics

Abstract view : 140 times
PDF - 57 times

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


 


Creative Commons License
MKB is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

 


View My Stats