An Experimental Study On Histopathological Effects Of Melatonin On Cyclosporin Induced Heart Damage

Abstract

Objectives: In recent studies, the damage of tissues caused by a Cyclosporine A (CyA) and the role of free oxygen radicals in this damage have been discussed widely. Melatonin, the most important indoleamine released from the pineal gland, is a free radical scavenger and antioxidant. In our study, histopathological investigation of the possible beneficial effects of melatonin on the cardiac damage caused by CyA was aimed. Materials and Methods: This study included 4 groups: Group 1: the control, Group 2: 4 mg/kg/day of melatonin intraperitoneal (i.p.), Group 3: 2 mg/kg/day of CyA subcutaneously (s.c.), and Group 4: 4 mg/kg/day of Melatonin i.p. plus 2 mg/kg/day of CyA s.c. administered group. Our study lasted for 28 days for each group. At the end of this period the rats were decapitated under terminal anesthesia. Their hearts were removed and embedded in paraffin blocks for sectioning. .At the end of the treatments cardiac tissue was treated for morphological (Hematoxylin and Eosin) analyses. Results: The sections of the control and melatonin groups were normal histologically. The myocard and the network among the myocardial tissue were uneven in the CyA administered group. In CyA administered group the localizations of the nuclei of the myocardial cells were not central. In some areas, the unity of the cells came to be damaged, and disintegration and vacuolization of the cytoplasm could be observed. Abundant cell infiltration was recognized in some areas. There was connective tissue increase from place to place and fibrosis could be observed especially around the cardiac fibrils and vessel walls. Another histopathoogical finding was the existence of small haemorrhagic fields.In the CyA plus Melatonin group, it was determined that all these histopathological findings were significantly diminished. Conclusion: As a result of this study, it has been concluded that the damage due to CyA is reversible and can be lowered by the administration of Melatonin.. ©2008, Firat University, Medical Faculty

Keywords

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Siklosporin A'ya Bağlı Kalp Hasarında Melatoninin Histopatolojik Etkileri Üzerine Deneysel Bir Çalışma

Öz

Amaç: Siklosporin A (CyA) yaygın kullanılan bir immunbaskılayıcıdır ve dokularda hasar oluşturduğu bilinmektedir. Son yıllarda yapılan çalışmalarda bu hasarda serbest oksijen radikallerinin rolü olduğu üzerinde durulmaktadır. Pineal bezden üretilen en önemli indolamin olan melatonin, serbest radikal süpürücüsü ve antioksidandır. Çalışmamızda CyA'ya bağlı kardiyak hasar üzerine melatoninin olası yararlı etkilerini histopatolojik olarak incelemeyi amaçladık. Gereç ve Yöntem: Bu çalışmada her biri 8'er sıçandan oluşan 4 grup oluşturuldu.1. grubumuz kontrol grubuydu. 2.grup 4mg/kg/gün intraperitoneal (i.p) melatonin verdiğimiz grup. 3. grup 10 mg/kg/gün subkutan (s.c) CyA uygulanan grup ve 4.grup 4mg/kg/gün/(i.p) melatonin ve 10 mg/kg/gün/(s.c) CyA uygulanan grup. Çalışmamız her grup için 28 gün sürdü. Bu sürenin sonunda denekler terminal anesteziyle öldürüldü. Çıkarılan kalp dokusu parafin bloklara gömülerek kesit alındı. Bu kesitler genel histolojik yapıyı gözlemlemek amacıyla Hematoksilen and Eosin (H-E) boyasıyla boyandı. Bulgular: Hem kontrol, hem de melatonin uyguladığımız grublarda kardiyak kesitler histolojik olarak normal görünümdeydi. CyA uygulanan sıçanlarda kalp kası tabakası ve yaptıkları ağ düzensiz izleniyordu. Hücrelerin nukleus yerleşimi merkezi değildi. Bazı alanlarda hücre bütünlüğünün bozulmaya başladığı, sarkoplazmada parçalanmaların ve vakuolizasyonların geliştiği fark ediliyordu. Bazı alanlarda bol miktarda hücre infiltrasyonu söz konusuydu. Yer yer bağ dokusu artmıştı ve özellikle kardiak fibrillerin etrafında ve damar çevrelerinde fibrozis izleniyordu. Bir diğer histopatolojik bulgu ise küçük çaplı hemorajik alanların varlığıydı. CyA ile birlikte melatonin uygulanan grubda bu histopatolojik bulgularımızın oldukça azaldığı tespit edildi. Sonuç: Bu çalışmanın sonucunda CyA'ya bağlı hasarın geri dönüşümlü olduğu ve melatonin uygulamasıyla bu hasarın önemli ölçüde azaltılabileceği sonucuna varıldı.©2008, Fırat Üniversitesi, Tıp Fakültesi

Anahtar Kelimeler

• Kalp, CyA, Melatonin, histopatoloji

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34. Kabul Tarihi:22.11.2007