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TAMOKSİFENİN SIÇAN KARACİĞERİNE ETKİSİ: IŞIK VE ELEKTRON MİKROSKOPİK İNCELEME

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Abstract (2. Language): 
The effects of tamoxifen on the rat liver; light and electron microscopical study. Tamoxifen is an antioestrogenic in a triphenylethylen group drug, common used for long time period mam-mary gland cancer treatment. Long time period consumption of this drug has a negative effect on the uterus and liver. For observation of the effect of tamoxifen on the liver morphology, tamoxifen was applied to the Sprague-Dawley female rats ip. 1.5 mg/kg for 3.5 months. Liver samples were examined at both light and electron microscopy level. Liver samples was showed that degeneration of the regulation of the celi cordon, bleeding are-as, increase of the connective tissue at Disse space at light microscopy level. Ultrastructural observations showed that alterations of the membrane and organelle structure, formation of vacuoles, and increase of glycogen and lipid droplets in the hepatocyte cytoplasm. As a result, application of the tamoxifen to the rats in these doses and time causes liver degeneration. As a result, patient treatedwifh tamoxifen because of the observation of the liver degeneration should be under control frequently.
Abstract (Original Language): 
Tamoksifen, meme kanserinin tedavisinde uzun süreli, en çok kullanılan trifeniletilen grubundan, en etkili antiöstrojenik ilaçtır. Bu ilacın uzun süreli kullanımına bağlı olarak karaciğer ve uterusta yan etkilere neden olduğu bilinmektedir. Karaciğer üzerine morfolojik etkilerini incelemek amacı ile Sprague-Dawley cinsi dişi sıçanlara 3.5 ay süreyle i.p olarak tamoksifen, 1.5 mg /kg olacak şekilde uygulandı. Alınan karaciğer biyopsi materyalleri ışık ve elektron mikroskopi düzeyinde incelendi. Işık mikroskopi düzeyinde karaciğer hücre kordon düzeninde bozulma, kanama odakları, Disse aralığı bağ dokusunda artış gözlendi. Hepatosit ince yapısında membran ve organellerin-de değişiklikler, glikojen içeriğinde ve lipid damlacıklarında ve vakuollerde artma gözlendi. Sonuç olarak, sıçanlarda bu süre ve dozda tamoksifen uygulanımı karaciğer hasarına sebep olmaktadır.
132-141

REFERENCES

References: 

1. Ahotupa M, Hirsimaki P, Pârssinen R and Mantyla E: Alterations of Drug Metabolising and Antioxidant Enz-yme Activities During Tamoxifen-induced Hepatocarci-nogenesis in the Rat. Carcinogenesis. 15: 863 (1994).
2. Al-Turk WA, Stohs SJ and Roche EB: Effect of Tamoxi-fen Treatment in Liver, Lung and Intestinal Mixedfuncti-on Oxidases in Male and Female Rats. Drug Metabolism and Disposition (1981).
3. Bertram G. Katzung: Estrogen & Progesterone Inhibitors & Antagonists. Basic &Clinical Pharmacology. 624 and 841. Sixth edition. Copyright (1995).
4. Blackburn AM, Amiel SA, Millis RR, Rubens RD: Ta-moxifen and Liver Damage Br. Med. J. Clin-Res Ed. 289: 288(1984).
5. Carthevy P, Nolan BM, Edwards RE Smith LL: The Role of Celi Proliferation in the promotion of Rat Liver Tu-mours by Tamoxifen. Cancer Letters. 106:163-169 (1996).
6. Dökmeci İ: Farmakoloji. İlaç uygulamalarında Temel Kavramlar. Cilt.2. Saray Medikal Yayıncılık (1996).
7. Dragan YP, Fahey S, Street K, Vaughan J, Jordan VC and Pitot HC: Studies of Tamoxifen as a Promoter of He-patocarcinogenesis in Female Fischer F344 Rats. Breast Cancer Research and Treatment. 31:11 (1994).
8. Dragan YP, Xu Y-D., and Pitot HC: Tumor Promotion as a Target for Estrogen / Antiestrogen Effects in Rat He-patocarcinogenesis. Preventive Medicine. 20:15-26. (1991).
9. Fernö M, Anderson C, Fallenius G and Idvall I: Oestro-gen Receptor Analysis of Paraffin Sections and Cytosol Samples of Primary Breast Cancer in Relation to Outco-me After Adjuvant Tamoxifen Treatment.Acta. Oncolo-gica.35:17 (1996).
10. Fornander T, Rutqvist LE, Wilking N, Carlström K and Schoultz B.: Oeslrogenic Effects of Adjuvant Tamoxifen in Postmenopausal Breast Cancer. Eur.J. Cancer 29:497 (1993).
11. Fornander T, Rutqvist LE:Adjuvant Tamoxifen and Se-cond Cancers. Lancet.I: 616 (1989).
12. Fornander T, Cedennark B, Mattsson A, Skoog L, Theve T, Askergren J, Rutquvist LE, Glas U, Silfversvvard C, Somell A, Wilking N, Hjalmar M-L: Adjuvant Tamoxi-fen in Early Breast Cancer: Occurrence of New Primary Cancers. The Lancet. 117 (1989).
13. Furr BJA, and Jordan VC: The Pharmacology and Clini-cal Uses of Tamoxifen Pharmac. Ther. 25:127 (1984).
14. Greaves P, Goonetilleke R, Nunn G, Topham J and Or-ton T: Two-Year Carcinogenicity Study of Tamoxifen in Alderley Park Wistar-derived Rats. Cancer Research. 53 :3919 (1993).
15. Hard GC, V/illiams GM, Iatropoulos MJ: Tamoxifen and Liver Cancer. The Lancet. 342: 444 (1993).
16. Hirsimaki P, Mantyla E, Hirsimaki Y and Mantyla M: The Effects of Tamoxifen and Toremifen on Rat Liver Ultrastructure and Peroxisomal Enzymes. ICEM 13-PA-RİS 1229(1994).
17. Hirsimaki P, Hirsimaki Y, Nieminen L.i and Joe PB: Ta-moxifen induces hepatocelluler carcinoma in rat liver: al year study with two antiestrogens. Arch. Toxicol . 67:49 (1993).
18. Jordan VC: Molecular Mechanisms of Antiestrogen Ac-tion in Breast Cancer .Breast Cancer Research and Treatment. 31:41 (1994).
29. Kim DJ, Han BS, Ahn B, Lee KK, Kang JS Tsuda H: Promotion Potential of Tamoxifen on Hepatocarcinoge-nesis in Female SD or F344 Rats Initiated with Diethy-lnitrosamine. Cancer Letters. 104:13 (1996).
20. Mani C and Kupfer D: Cytochrome P-450 mediated Ac-tivation and Irreversible Binding of the Antiestrogen Ta-moxifen to Proteins in Rat and Human Liver: Possible
Güven A., Ercan F .
Involvement of Flavin-containing Monooxygenases in Tamoxifen Aclivation. Cancer Research. 51: 6052 (1991).
21. Mani C, Gelboin HV, Park SS, Pearce R, Parkinson A and Kupfer D: Metabolism of the Antimammary Cancer Antiestrogenic Agent Tamoxifen. Drug Metabolism and Disposition. 21:645 (1993).
22. Morrow M, Jordan VC: Risk Factors and the Prevention of Breast Cancer vvith Tamoxifen. Cancer Surveys. 18:211 (1993).
23. Robertson JFR, Ellis IO, Nicholson RI, Robins A, Bell J.
and Blamey RW: Cellular Effects of Tamoxifen in Primary Breast Cancer. Breast Cancer Research and Treatment 20:117(1991).
24. Taylor CM, Blanchard B and Zava DT: Estrogen Recep-tor-Mediated and Cytotoxic Effects of the Antiestrogens Tanıoxifen and 4-Hydroxytamoxifen. Cancer Resarch. 44: 1409 (1984).
25. Williams GM, Jatropoulos MJ, Djordjevic MV and Kal-tenberg OP: The Triphenylethylene Drug Tamoxifen is a Strong Liver Carcinogen in the Rat. Carcinogenesis. 14: 315 (1993).

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