ERKEN DÖNEM FETUSLARIN KALPLERİNDE SEPTAL GELİŞİM ÜZERİNE ADRİAMYCİN İNTERATOJENİK ETKİSİ

Abstract

Özofageal atrezi sıklıkla kardiyovasküler ve diğer malformasyonlar ile ilişkilidir. Bu çalışmada kalp gelişiminin sıçanlarda oluşturulan özofageal atrezi modelinde anormal olabileceği sınandı. Zaman kontrolu yapılarak çiftleştirilen gebe sıçanlara, gebeliğin 6-9. günlerinde 2 mg/kg adriamycin intraperitoneal olarak verildi. Kalp malformasyonları 13 günlük erken dönem fetuslarda mikroskopik olarak incelendi. Adriamycine maruz kalmış anne sıçanların embriyolarının (erken fetuslarını) çoğunda adriamycin rezorpsiyona neden olmuştu ve sadece yedi embriyo elde edilebildi. Kontrol fetuslar hiçbir kalp malformasyonuna sahip değilken adriamycine maruz kalmış yedi fetusun beşinde, özofagus atrezisi yanında interatriyal ve interventriküler septal defektler görüldü. Sonuç olarak, gebe sıçanlara adriamycin uygulaması embryolarda özofageal atrezi ve kalp malformasyonlarının oluşmasına sebep olur.

Keywords

• Adriamycin, kalp, kusurluluk, embriyo, gelişim

Teratogenic Effect of Adriamycin on Septal Development of Early Fetal Heart

Abstract

Esophageal atresia is often associated with cardiovascular and other malformations. The present study tests the heart development which may be abnormal in the rat model of esophageal atresia. Time-mated pregnant rats received 2 mg/kg adriamycin intraperitoneally on days 6-9 of gestation. The heart malformations were investigated on day 13 of gestation under the microscope in early term fetuses. Adriamycin caused resorption of most embryos (or early fetuses) and only seven embryos obtained from adriamycin received dams. Control fetuses had no heart malformations, whereas five of the seven fetuses exposed to adriamycin had interatrial and interventricular septal defects besides esophageal atresia. As a result, adriamycin administration to pregnant rats, results of esophageal atresia and cardiac malformations in embryos.

Keywords

• Adriamycin, heart, malformation, embryo, development

References

1. Theiler K. The House Mouse. Springer Verlag, Ber- lin 1972; pp 21-63.
2. Chittmittrapap S, Spitz L, Kiely EM, et al. Oeso- phageal atresia and associated anomalies. Arch Dis Child 1989; 64: 364-368.
3. Rokitansky A, Kolankaya A, Bichler B, et al. Analy- sis of 309 cases of esophageal atresia for associ- ated congenital malformations. Am J Perinatol 1994; 11: 123-128.
4. Cui Y, Xu Q, Chow PK, et al. Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment. Biomaterials 2013; 34: 8511-8520.
5. Dawrant MJ, Giles S, Bannigan J, et al. Adriamycin produces a reproducible teratogenic model of vertebral, esophageal, renal, and limb anomalies in the mouse. J Pediatr Surg 2007; 42: 1652-1658.
6. Özdamar S, Ülger H, Çetin Sorkun H. Influence of adriamycin on nature and position of notochord. Erciyes Tıp Dergisi 2005; 27: 70-74.
7. Qi BQ, Merei J, Farmer P, et al. Cardiovascular mal- formations in rat fetuses with oesophageal atresia and tracheo-oesophageal fistula induced by adria- mycin. Pediatr Surg Int 1997; 12: 556-564.
8. Xia H, Otten C, Migliazza L, et al. Tracheobronchial malformations in experimental esophageal atresia. J Pediatr Surg 1999; 34: 536-539.

9. Otten C, Migliazza L, Xia H, et al. Neural crest- derived defects in experimental esophageal atresia. Pediatr Res 2000; 47: 178-178.
10. Orford JE, Cass DT. Dose response relationship between adriamycin and birth defects in a rat model of VATER association. J Pediatr Surg 1999; 34: 392-398.
11. Billingham ME. Pharmacotoxic myocardial dis- ease: an endomyocardial study. Heart Vessels 1985; suppl 1: 278-282.
12. Zbinden G, Brandle E, Pfister M. Modification of adriamycin toxicity in rats fed a high fat diet. Agents Actions. 1977; 7: 163-170.
13. Harris PA, Gross JF. Preliminary pharmacokinetic model for adriamycin (NSC-123127). Cancer Chemother Rep 1975; 59: 819-825.
14. Singal K, Li T, Kumar D, et al. Adriamycin-induced heartfailure: mechanism and modulation. Mol Cell Biochem 2000; 207: 77-86.
15. Minow RA, Benjamin RS, Lee ET, Gottlieb JA. Adria- mycin cardiomyopathy-risk factors. Cancer 1977; 39:1397-1402.
16. van Helden PD, Wild IJ. Effects of adriamycin on heart and skeletal muscle chromatin. Biochem Pharmacol 1982; 31: 973-977.
17. Lewis W, Galizi M, Puszkin S. Compartmentaliza- tion of adriamycin and daunomycin in cultured chick cardiac myocytes. Effects on synthesis of contractile and cytoplasmic proteins. Circ Res 1983; 53: 352-362 .
18. Rabkin SW, Sunga P. The effect of doxorubicin (adriamycin) on cytoplasmic microtubule system in cardiac cells. J Mol Cell Cardiol 1987; 19: 1073- 1083.
19. Morini F, Cozzi DA, Ilari M, et al. Pattern of cardio- vascular anomalies associated with esophageal atresia: support for a caudal pharyngeal arch neu- rocristopathy. Pediatr Res 2001; 50: 565-568.