Siklosporin-A verilen sıçanların böbrek korteksleri üzerine E vitamini etkilerinin ve elektron mikroskopik düzeylerde incelenmesi
Küçük Resim Yok
Tarih
2000
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
ÖZET Cs-A; günümüzde, organ transplantasyonları ve immün sistem hastalıklarında kullanılan, güçlü immünosüpresif bir ajandır. Etkisini, T helper lenfositlerden özellikle IL-2 ve diğer bazı sitokinlerin (IL-3, IL-4, TNF-a, y-interpheron) sentezini selektif bir şekilde inhibe ederek gösterir. Ancak nefrotoksik etkisi, ilacın kullanım alanına sınırlılık getirmiştir. Son yıllarda, antioksidanlarla, bu nefrotoksi siteyi önlemeye yönelik çalışmalar önem kazanmıştır. Bu çalışmada; Cs-A'nın böbrek korteksinde oluşturduğu hasarda, Cs-A'yı inhibe eden antioksidan E vitamininin morfolojik açıdan bir koruyuculuk sağlayıp sağlamayacağı, ışık ve elektron mikroskopik düzeylerde incelendi. Bunun için, 25 adet Sprague-Dawley türü erkek rat, ağırlıklarına göre, her biri 5'er denek içerecek şekilde 5 gruba ayrıldı. Tüm gruplara; aynı biyolojik ve fizyolojik koşullar uygulandı. I. grup kontrol grubu olarak ayrılıp, diğer 4 gruba 5 mg/kg/gün Cs-A intraperitoneal olarak 8 hafta boyunca verildi. I. ve II. grubun böbrek korteks biyopsi materyalleri 8. haftanın sonunda; III. grubun böbrek korteks biyopsi materyalleri reversibilite için 6 hafta bekletilerek, 14. haftanın sonunda; IV. grubun böbrek korteks biyopsi materyalleri, 5 mg/kg/gün Cs-A ile birlikte 5 mg/kg/gün E vitamini verilerek 8. haftanın sonunda; V. grubun böbrek korteks biyopsi materyalleri, 8 haftalık 5 mg/kg/gün Cs-A veriminden sonra ve 6 hafta sadece 5 mg/kg/gün E vitamini verilerek 14. haftanın sonunda alınarak ışık ve elektron mikroskopik gözlemler için işlemlendirildi. Malpighi cisimciklerinde; kapsül ve ortak bazal membranlarda kalınlaşma, parietal yaprak hücresi ve cisimcik içerisinde yer alan hücrelerde gerileme, dejenerasyon görüldü. 53Tübül değişikliklerine daha çok proksimal tübüllerde rastlanmakta olup, bu değişiklikler; dejenerasyon ve rejenerasyon şeklinde gözlendi. Dejenerasyon; bazal membranlarda kalınlaşma, fırçamsı kenarlarda kayıp, vakuolizasyon, düz endoplazmik retikulum dilatasyonu, çok sayıda ve farklı büyüklükte lizozomlar şeklinde görülürken, dağılmış bazı tübül epitel hücrelerinin proliferasyonu da yeni tübüllerin ortaya çıkmasını sağlayarak rejenerasyon sahalarım oluşturuyordu. İnterstisyel bağ dokuda; damarların genellikle kontraksiyon halinde olduğu, bağ dokuda hücre ve kollagen lif artışının ise böbrek parankiminin azalmasıyla ters orantılı olduğu gözlendi. Sadece Cs-A alan II. grup deneklerde görülen bozuklukların, III. grup deneklerde de görülmesinin, Cs-A'mn bazı dokularda birikimi nedeniyle; Cs-A ile birlikte E vitamini alan IV. grup deneklerde, bu bozuklukların görülmeyişinin, E vitamininin Cs-A'yı inhibe ettiğinden; Cs-A'mn kesilip E vitamininin verildiği V. grup deneklerde ise, dokularda depolanmış Cs-A'mn organizmaya verilişi devam ettiğinden dolayı IV. gruba oranla daha çok hasara uğramış olduğunu düşündük. Bu nedenle; Cs-A'nın uzun süre kullanılması gereken durumlarda, aynı dönemde tedaviye antioksidan eklenmesi ile Cs-A'mn neden olduğu böbrek hasarının minimal düzeyde tutulabileceği kanısındayız. 54
SUMMARY ULTRASTRUCTURAL EFFECTS OF VITAMIN E ON KIDNEY CORTEX OF RATS IN CYCLOSPORIN-A ADMINISTRATION. Nowadays Cs-A is a potent immunosuppressive agent used for organ transplantations and immune system disorders. It shows its effect by selectively inhibiting synthesis of especially IL-2 and some other cytokines ( IL-3, IL-4, TNF-a, y- interpheron) from T helper lymphocytes. But its nephrotoxic effect limits its use. In the last years, many researches to prevent this nephrotoxicity by the antioxidants gained importance. In this study; on light and electron microscopical level, it has been examinated whether vitamin E which inhibits Cs-A, provides morphological protection for the renal cortical damage produced by Cs-A. For this aim 25 Sprague-Dawley species of male rats are divided into 5 groups each consisting of 5 rats according to their weights. Each group is kept under same physiological and biological conditions. First group is selected as control group, to the rest 4 group 5 mg/kg/day Cs-A was administered intraperitonealy during 8 weeks. Renal cortical biopsy materials of the second and third group were taken at the end of the 8th week; renal cortical biopsi materials of third group was taken at the end of 14th week after they have been kept for reversibility for 6 weeks; biopsy materials of fourth group was taken at the end of 8th week after administration of 5 mg/kg/day vitamin E together with 5 mg/kg/day Cs-A; renal cortical biopsy materials of the fifth group were taken at the end of the 14th by administration of 5 mg/kg/day vitamin E during 6 weeks after administration of 8 weeks of 5 mg/kg/day Cs-A, these biopsy materials are processed for light and electron 55microscopical examination. In the Malpighi corpuscules, thickening of capsule and basement membrane, degeneration and regression of the cells of the parietal sheat and corpuscules cells was observed. Tubule changes were mostly encountered in the proximal tubules and these were seen as degeneration and regeneration. While this degeration was being seen as the thickening of basement membrane, loss of brush border, vacuolization, dilatation of the smooth endoplasmic reticulum, increasement of lysosomes in number and size, proliferation of some of scattered epithelial cells of tubules formed the regeneration areas by providing appearance of new tubules. In the interstitial connective tissue it was observed that vessels were generally seem to be in contractile state and in inverse proportion with the renal parenchymal loss there was an increase in the cells and collagen fibers of connective tissue. We thought that observance of the same disorders in the third group as seen in the only Cs-A administered second group, was due to accumulation of Cs-A in some tissues; inobservance of these disorders in the fourth group where vitamin E was administered together with the Cs-A was because of the inhibition Cs-A by vitamin E; in the fifth group where vitamin E administered after the cease of administration of Cs-A, there was more damage in proportion to the fourth group because of the release of Cs-A deposited in tissues into the organism. We conclude that, in the cases where Cs-A is needed to be used in long term with the addition of antioxidants to treatment in the same period, it can be minimize the renal damage produced by Cs-A. 56
SUMMARY ULTRASTRUCTURAL EFFECTS OF VITAMIN E ON KIDNEY CORTEX OF RATS IN CYCLOSPORIN-A ADMINISTRATION. Nowadays Cs-A is a potent immunosuppressive agent used for organ transplantations and immune system disorders. It shows its effect by selectively inhibiting synthesis of especially IL-2 and some other cytokines ( IL-3, IL-4, TNF-a, y- interpheron) from T helper lymphocytes. But its nephrotoxic effect limits its use. In the last years, many researches to prevent this nephrotoxicity by the antioxidants gained importance. In this study; on light and electron microscopical level, it has been examinated whether vitamin E which inhibits Cs-A, provides morphological protection for the renal cortical damage produced by Cs-A. For this aim 25 Sprague-Dawley species of male rats are divided into 5 groups each consisting of 5 rats according to their weights. Each group is kept under same physiological and biological conditions. First group is selected as control group, to the rest 4 group 5 mg/kg/day Cs-A was administered intraperitonealy during 8 weeks. Renal cortical biopsy materials of the second and third group were taken at the end of the 8th week; renal cortical biopsi materials of third group was taken at the end of 14th week after they have been kept for reversibility for 6 weeks; biopsy materials of fourth group was taken at the end of 8th week after administration of 5 mg/kg/day vitamin E together with 5 mg/kg/day Cs-A; renal cortical biopsy materials of the fifth group were taken at the end of the 14th by administration of 5 mg/kg/day vitamin E during 6 weeks after administration of 8 weeks of 5 mg/kg/day Cs-A, these biopsy materials are processed for light and electron 55microscopical examination. In the Malpighi corpuscules, thickening of capsule and basement membrane, degeneration and regression of the cells of the parietal sheat and corpuscules cells was observed. Tubule changes were mostly encountered in the proximal tubules and these were seen as degeneration and regeneration. While this degeration was being seen as the thickening of basement membrane, loss of brush border, vacuolization, dilatation of the smooth endoplasmic reticulum, increasement of lysosomes in number and size, proliferation of some of scattered epithelial cells of tubules formed the regeneration areas by providing appearance of new tubules. In the interstitial connective tissue it was observed that vessels were generally seem to be in contractile state and in inverse proportion with the renal parenchymal loss there was an increase in the cells and collagen fibers of connective tissue. We thought that observance of the same disorders in the third group as seen in the only Cs-A administered second group, was due to accumulation of Cs-A in some tissues; inobservance of these disorders in the fourth group where vitamin E was administered together with the Cs-A was because of the inhibition Cs-A by vitamin E; in the fifth group where vitamin E administered after the cease of administration of Cs-A, there was more damage in proportion to the fourth group because of the release of Cs-A deposited in tissues into the organism. We conclude that, in the cases where Cs-A is needed to be used in long term with the addition of antioxidants to treatment in the same period, it can be minimize the renal damage produced by Cs-A. 56
Açıklama
Tıpta Uzmanlık
Anahtar Kelimeler
Morfoloji, Morphology
