Estrogen-induced hepatotoxicity in rats
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Department of Human Anatomy, Medical University, Lublin, Poland
Department of Oncology, Medical University, Lublin, Poland
Department of Animal Anatomy and Histology, University of Life Sciences, Lublin, Poland
Department of Pulmonology, Oncology and Allergology, Medical University, Lublin, Poland
J Pre Clin Clin Res. 2012;6(1):10–13
Estrogens, primarily in the form of oral contraceptives, are responsible for several pathological conditions, including hepatocellular changes, cholestatic injury, vascular lesions and adenomas. The aim of this study was to determine the influence of estrogen on the morphology of the liver. The experiment was conducted on female Wistar rats. Oestradiolum benzoicum was administered intramuscularly for 8 weeks in 3 different doses (0.00075-0.003 mg/kg). All animals were sacrificed after 9 weeks and livers were examined macroscopically, and on the histological and ultrastructural levels. The most common features were as follows: peliosis hepatis, fatty changes, adenomas, nodular regenerative hyperplasia, canalicular cholestasis, and mitochondrial damage. It can be concluded that long-term estrogen administration causes toxic damage in the liver of rats.
1. Mitchel JR, Nelson SD, Thorgeirson SS. Metabolic activation: biochemical basis for many drug-injuries. Progr Liver Dis. 1976; 5: 259-265.
2. Kreek MJ. Female sex steroids and cholestasis. Semin. Liver Dis. 1987; 7: 8-23.
3. Losordo DW, Isner JM. Estrogen and angiogenesis: A reviev Arterioscler Thromb Vasc Biol. 2001; 21: 6-12.
4. Van Erpecum KJ, Janssens AR, Kreuning J, Ruiter DJ, Kroon HM, Grond AJ. Generalized peliosis hepatis and cirrhosis after long-term use of oral contraceptives. Am J Gastroenterol. 1988; 83: 572-575.
5. Edmondson HA, Henderson B, Beneton B. Liver-cell adenomas associated with use of oral contraceptives. N Engl J Med. 1976; 294: 470-472.
6. Farrell GC. Drug-induced liver disease. Edinburgh, Scotland: Churchill Livingstone.
7. Hannaford PC, Kay CR. The risk of serious illness among oral contraceptive users: evidence from the RCGP’s oral contraceptive study. Br J Gen Pract. 1998; 48: 1657-1662.
8. Lidegaard O, Edstrom B, Kreiner S. Oral contraceptives and venous thromboembolism. A case-control study. Contraception 1998; 57: 291- 301.
9. Wille AG, DiSaia PJ. Hormones and breast cancer. Am J Surg 1989; 157: 438-442.
10. Hankinson SE, Stampfer MJ. Estrogens and breast cancer. Salud Publica Mex 1997; 39: 370-380.
11. Varma TR. Sex steroids and cancer in older women. Drugs Aging 1992; 2: 174-195.
12. Jellinek G. Changes in the endometrium from the use of hormonal preparations and hormonal contraceptives. Arkh Patho. 1978; 40: 36-45.
13. Hartmann BW, Huber JC. The mythology of hormone replacement therapy. Br J Obstet Gynecol 1997;104: 163-168.
14. Ishak KG, Zimmerman HJ. Hepatotoxic effects of the anabolic androgenic steroids. Semin.Liver Dis 1987; 7: 230-236.
15. Shmid M. Contraceptives and the liver. Leber Magen Darm 1981; 11: 216-226.
16. Tsung SH, Han D, Loh WP, Lin JI. Budd-Chiari syndrome in women taking oral contraceptives. Ann Clin Lab Sci 1980; 10: 518-522.
17. Patt V. Liver function in hormonal contraception. Fortschr Med 1976; 94: 1900-1906.
18. Paumgartner G, Paumgartner D. Damage to liver and biliary tracts by long-term drug therapy. MMW Munch Med. Wochenschr 1980; 5: 1223-1225.
19. Ishak KG, Rabin L. Benign tumors of the liver. Med Clin North Am 1975; 59: 995-1013.
20. Lance RP, Pharm D. Drug-induced allergic hepatitis. Semin. Liver Dis 1990; 10 (4): 305-315.
21. Górska P. Principles in laboratory animals research for experimental purpose. Med Sc. Monit 2000; 6: 171-180.
22. Wisse E. Ultrastructure and function of Kupffer cells and other sinusoidal cells in the liver. In Kupffer Cells and Other Sinusoidal Cells. Elsevier North-Holland, Biomedical Press 1977: 33.
23. Bardadin KA, Desment VJ. Ultrastructural observations on sinusoidal endothelial cells in chronic active hepatitis. Histopathology 1985; 9: 171-181.
24. DeLeve LD. Vascular liver diseases. Curr Gastroenterol Rep 2003; 5: 63-70.
25. Durakis S, Tolis G. Sex hormonal preparations and the liver. Eur J Contracept. Reprod Health Care 1998; 3: 7.
26. Brooks SHE, Haggis GH. Scanning electron microscopy of rat’s liver. Application of freeze-fracture and freeze-drying technique. Lab Inve. 1973; 29: 60-64.
27. Lennert K, Mohri N, Stein H, Kaiserling E, Muller-Hemerlink HK. Malignant Lymphomas Other Than Hodgkin’s Disease. Springer Verlag, 1978 Berlin-Heidelberg-New York.
28. Radzikowska E, Maciejewski R, Janicki K, Madej B, Wójtowicz Z. The relationship between estrogen and the development of liver vascular disorders. Annales Sec D LVI 2001; 29: 189-195.
29. Valla DC. Vascular disorders of the liver. Acta Gastroenterol Belg 2003; 66: 294-297.
30. Taxy JB. Peliosis: a morphologic curiosity becomes an iatrogenic problem. Hum Pathol. 1978; 9(3): 331-40.
31. Willam M, Lee MD. Drug-induced hepatotoxicity. The New England Journal of Medicine 1995; 333: 1118-1127.
32. Wang SY, Ruggles S, Vade A, Newman BM, Borge MA. Hepatic rupture caused by peliosis hepatis. J. Pediat. Surg 2001; 36: 1456-1459.
33. Poulsen H, Winkler K. Liver disease with periportal sinusoidal dilatation. Digestion 1973; 8: 112-160.
34. Schaff Z, Szekely E, Jaray B, Kiss A. Pathology of liver tumors. Orv Hetil 2004; 145: 368-374.