Lapatinib’in s??an over ve uterus dokular? üzerine olan etkilerinin ???k ve elektron mikroskobik düzeyde ara?t?r?lmas?

摘要

Ama?: Moleküler onkolojideki geli?meler sonucunda hedeflenmi? anti-kanser tedavisinde kullan?lmaya ba?lanan bir?ok ila?, hücre resept?rleri ve hücre i?i sinyal molekülleri ile etkile?erek tüm?r hücrelerinin ?o?almas?n? durdurmaktad?r. Bu hede?erin ?zyolojik g?revleri nedeniyle tedavi s?ras?nda yan etkiler geli?mektedir. Hedefe y?nelik tedavide kullan?lan ila?lardan biri olan Lapatinib hücre i?ine girerek epidermal büyüme fakt?rü ve resept?rüne ba?l? tirozin kinaz aktivitesini inhibe etmektedir. ?al??mam?zda Lapatinib’in s??an uterus ve over dokular?nda yol a?abilece?i de?i?ikliklerin biyokimyasal, ???k ve elektron mikroskobik düzeyde incelenmesi ama?land?. Gere? ve Y?ntem: 24 adet Wistar cinsi di?i s??an 3 gruba ayr?larak, deney gruplar?na s?ras?yla 30 mg/kg ve 75 mg/kg Lapatinib, kontrol grubuna ise ayn? miktarda distile su gavaj yoluyla, günde 2 kez 14 gün boyunca uyguland?. Deney sonunda hayvanlardan kan ?rnekleri al?narak serum ?stradiol, progesteron, FSH ve LH seviyeleri ?l?üldü. Uterus ve over doku ?rnekleri ???k ve elektron mikroskobik doku haz?rlama y?ntemlerine uygun olarak haz?rland?. Dokulardan elde edilen kesitler, Jeol JEM 1400 TEM ve Olympus BX 50 ???k mikroskoplar?nda de?erlendirildi. Bulgular: Deney gruplar?na ait s??anlarda ?stradiol ve progesteron seviyelerinde azalma yan?nda ???k ve elektron mikroskobik kesitlerde, endometriyumda stromal hücreler ve bezlerde, overlerde ise oosit, granüloza hücreleri ile interstisyel hücrelerde yap?sal de?i?ikliklerin geli?ti?i ve bu de?i?ikliklerin yüksek doz grubunda daha belirgin oldu?u g?zlendi. Sonu?: Lapatinib gibi hedefe y?nelik tedavilerde kullan?lan ila?lar?n hedefledi?i resept?rler ve sinyal moleküllerinin blokaj?na ba?l? olarak bunlar?n kullan?ld??? doku ve organlar?n yap? ve fonksiyonlar?nda de?i?iklikler geli?ebilece?i kanaatine var?ld?. Purpose: Many drugs, started to be used in targeted anti-cancer treatment as a result of advances in molecular oncology, stop proliferation of tumor cells via interacting with cell receptors and intracellular signaling molecules. Because of physiological functions of these targets, adverse effects develop during therapy. Lapatinib is one of the drugs used in targeted therapies, enters into the cell and inhibits the activity of epidermal growth factor and receptor-linked tyrosine kinase. Our study aimed to investigate changes in uterine and ovarian tissues of rats caused by Lapatinib at biochemical, light and electron microscopic levels. Materials and Methods: 24 female Wistar rats were divided into 3 groups, 30 mg/kg and 75 mg/kg Lapatinib to experimental groups, and same amount of distilled water to the control group were applied twice a day by gavage during 14 days. Blood samples were collected for estradiol, progesterone, FSH and LH serum levels. Uterine and ovarian tissue samples were prepared for light and electron microscopic examinations and evaluated by Jeol JEM 1400 TEM and Olympus BX 50 light microscope. Results: Besides the reduction of estradiol and progesterone levels in experimental groups, structural changes in stromal cells and glands of endometrium, oocyte, granulose cells and interstitial cells of ovaries were observed, and it was observed that these changes were more prominent in high dose group. Conclusion: Drugs that are used in targeted therapies, such as Lapatinib, can cause structural and functional changes in tissues and organs depending on blockage of receptors and targeted signal molecules.