Publication: Sıçanlarda deneysel olarak geliştirilen kronik renal yetmezliğinin tedavisinde anjiyotensin dönüştürücü enzim inhibitörlerinin ve anjiyotensin reseptör antagonistlerinin antioksidan tedavi ile karşılaştırılması
Abstract
Bu çalışmada kronik böbrek yetmezliğinin (KBY) yaptığı hemodinamik ve oksidatif değişiklikleri inceleyerek ADE İ kaptopril ile anjiyotensin reseptör antagonisti valsartanın bu değişiklikler üzerindeki etkilerinin güçlü bir antioksidan N-asetilsistein (NAC) ile karşılaştırılması amaçlanmıştır. Bu amaçla Wistar albino sıçanlarda kronik böbrek yetmezliği oluşturuldu. Tedavili gruplarda hayvanlara 45 gün süresince günde bir kez kaptopril, valsartan ve N-asetil sistein uygulanırken KBY grubuna da SF verildi. Deney boyunca birer haftalık aralıklarla hayvanların kan basıncı ve kalp hızları takip edildi. Deney sonunda 24 saatlik idrarları toplanan sıçanlar dekapite edilerek kan ve doku örnekleri alındı. İdrar örneklerinde, elektrolit ve kreatinin düzeyleri; kan örneklerinde sitokin (İL-1β, İL-6, İL-10, TNF-α), LDH, elektrolit, BUN ve kreatinin düzeyleri, lökosit apoptozisi, dokularda glutatyon, malondialdehit ve kollajen düzeyleri ve myeloperoksidaz aktivitesi tayin edildi. Sonuçlar incelendiğinde KBY grubunda bulunan sıçanların kalp atım hızları ve kan basınçları anlamlı olarak arttığı, tedavili gruplarda ise bu değerlerin KBY grubuna göre anlamlı olarak azaldığı görüldü. KBY grubunda idrar hacminin, idrar kreatinin ve elektrolit düzeylerinin azaldığı, lökositler apoptozis oranının arttığı, serumda kreatinin, BUN, LDH, TNF-α, İL-1β, İL-6 ve elektrolit düzeylerinin yükseldiği, İL-10 düzeylerinin azaldığı gözlenirken tüm dokularda malondialdehit, ve kollajen düzeyleri ile myeloperoksidaz aktivitesinin arttığı, glutatyon düzeylerinin ise azaldığı bulundu. Kronik böbrek yetmezliğinin serum ve dokularda neden olduğu tüm değişiklikler kaptopril, valsartan ve NAC ile önlenirken NAC ile kombine uygulamada daha anlamlı bir düzelme olduğu saptandı. Bu sonuçlar, KBY’nin oksidan hasara neden olduğunu, bu hasarın da hipertansiyona zemin hazırladığını, buna karşılık kaptopril ve valsartanın N-asetilsistein ile kombine uygulamalarının KBY’de görülen değişiklileri önleyerek mortalite ve morbidite riskini azaltabileceklerini düşündürmektedir.
The aim of this study is to compare the effects of angiotensin converting enzyme inhibitor, captopril, and angiotensin receptor antagonist, valsartan, on the chronic renal failure (CRF) related hemodynamic and oxidative damage parameters with that of the antioxidant N-acetyl-L-cysteine (NAC). In Wistar albino rats, following the development of CRF, saline, Captopril (1 mg/ kg), Valsartan (1 mg/ kg) and NAC (150 mg/ kg) were given once a day as single agents or in combinations. Blood pressure and heart rate of the rats were monitored at weekly intervals throughout the follow-up period. At the end of 45 days, 24-hour urine was collected to measure the electrolytes and creatinine and the rats were decapitated. Trunk blood was taken for the determination of IL-1β, IL-6, IL-10, TNF-α, leukocyte apoptosis, LDH, electrolytes, BUN and creatinine, while the brain, heart, aorta and kidney samples were obtained to measure glutathione, malondialdehyde (MDA) and collagen levels, and myeloperoxidase activity (MPO). In saline-treated CRF group, heart rate and blood pressure were increased, while in the other treatment groups these increases were significantly reversed. In saline-treated CRF group, there were decreases in the urine volume, creatinine and electrolyte levels, while leukocyte apoptosis, serum creatinine, BUN, LDH, IL-1β, IL-6, TNF-α and electrolyte levels were elevated with a concomitant decrease in IL-10 levels. Moreover, in all the examined tissues, MDA and collagen levels, MPO activity were increased significantly, and the glutathione levels were depressed. On the other hand, these biochemical changes were reversed in captopril, VAL or NAC-treated groups, while the combination of captopril or valsartan with NAC was found to be more effective. The present results indicate that these agents can be considered as choices of treatment in reducing mortality and morbidity in CRF.
The aim of this study is to compare the effects of angiotensin converting enzyme inhibitor, captopril, and angiotensin receptor antagonist, valsartan, on the chronic renal failure (CRF) related hemodynamic and oxidative damage parameters with that of the antioxidant N-acetyl-L-cysteine (NAC). In Wistar albino rats, following the development of CRF, saline, Captopril (1 mg/ kg), Valsartan (1 mg/ kg) and NAC (150 mg/ kg) were given once a day as single agents or in combinations. Blood pressure and heart rate of the rats were monitored at weekly intervals throughout the follow-up period. At the end of 45 days, 24-hour urine was collected to measure the electrolytes and creatinine and the rats were decapitated. Trunk blood was taken for the determination of IL-1β, IL-6, IL-10, TNF-α, leukocyte apoptosis, LDH, electrolytes, BUN and creatinine, while the brain, heart, aorta and kidney samples were obtained to measure glutathione, malondialdehyde (MDA) and collagen levels, and myeloperoxidase activity (MPO). In saline-treated CRF group, heart rate and blood pressure were increased, while in the other treatment groups these increases were significantly reversed. In saline-treated CRF group, there were decreases in the urine volume, creatinine and electrolyte levels, while leukocyte apoptosis, serum creatinine, BUN, LDH, IL-1β, IL-6, TNF-α and electrolyte levels were elevated with a concomitant decrease in IL-10 levels. Moreover, in all the examined tissues, MDA and collagen levels, MPO activity were increased significantly, and the glutathione levels were depressed. On the other hand, these biochemical changes were reversed in captopril, VAL or NAC-treated groups, while the combination of captopril or valsartan with NAC was found to be more effective. The present results indicate that these agents can be considered as choices of treatment in reducing mortality and morbidity in CRF.