Publication: Myrtus communis (mersin) bitkisinin üriner sistem taş hastalığı üzerine etkisinin incelenmesi
Abstract
1.ÖZETAmaç: Üriner sistem taş hastalığı (USTH), böbrek fonksiyon bozukluğuna ve kalıcı renal hasara yol açabilen önemli bir ürolojik hastalıktır. Bu çalışmada, Myrtus communis (MC) bitkisinin taş oluşumunu engelleyici ve taşa bağlı hasara karşı tedavi edici etkilerinin incelenmesi amaçlanmıştır.Gereç ve Yöntem: Üç aylık erkek, 250-300 g ağırlığında 32 adet Wistar albino sıçan randomize edilerek kontrol, etilen glikol (EG), MC koruyucu tedavili ve MC tedavili olmak üzere dört gruba (n=8) ayrılmıştır. Taş hastalığı modeli için sıçanlara %0,75 EG içeren içme suyu 8 hafta süre ile verilmiştir. Çalışma sonunda hayvanlar metabolik kafeslere alınarak idrarda kalsiyum, oksalat, sitrat ve kreatinin tayinleri için 24 saatlik idrar örnekleri toplanmıştır. Böbrek dokularında histolojik incelemeler ile osteopontin, N-asetil-β-glukozaminidaz (NAG), myeloperoksidaz (MPO), kaspaz-3 aktivitesi, oksidatif DNA hasarı (8-OHdG) tayinleri yapılmıştır. Bulgular: 24 saatlik idrar örneklerinde EG grubunda kalsiyum, sitrat ve kreatinin düzeyleri azalırken, oksalat düzeyleri artmış, tedavi gruplarında ise kontrol seviyelerine geri dönmüştür. Dokuda MPO, 8-OHdG, kaspaz-3 ve NAG aktivitesi anlamlı olarak artmış ve iki tedavi grubunda da bu değişiklikler geri çevrilmiştir. Histolojik bulgular da biyokimyasal bulguları desteklemiştir. Sonuç: Myrtus communis koruyucu veya tedavi edici ajan olarak kullanıldığında, muhtemelen antioksidan özellikleri ile kristal formasyon ve agregasyonu nedeniyle oluşan kristalüri ve böbrek hasarını önleyebilir. Böylece MC, oksidatif böbrek hücre hasarı ve böbrek taşı oluşumunu önlemede klinik bir uygulama alanına sahip olabilir.İÇİNDEKİLERTEZ ONAYIiBEYANiiTEŞEKKÜRiiiİÇİNDEKİLERivKISALTMA VE SİMGELER LİSTESİviiŞEKİL LİSTESİviiiTABLO LİSTESİixRESİM LİSTESİx1.ÖZET12.SUMMARY23.GİRİŞ VE AMAÇ34.GENEL BİLGİLER84.1.Taş Oluşum Mekanizmaları84.1.1.Süpersatürasyon94.1.2.Nükleasyon ve kristal formasyon104.1.3.Kristal agregasyonu104.1.4.Kristal retansiyonu114.1.5.Randal plakları124.2.Taş Oluşumunu Uyarıcı ve Baskılayıcı Moleküller134.3.Etilen Glikol ve Üriner Sistem Taş Modeli184.4.Myrtus communis – Mersin Bitkisi195.GEREÇ VE YÖNTEM235.1.Myrtus communis bitki ekstresinin hazırlanması235.2.Çalışma Grupları235.3.Biyokimyasal İncelemeler255.3.1.İdrarda kalsiyum, sitrat, oksalat ve kreatinin değerlerinin ölçümü255.3.2.Oksidatif DNA hasarı ölçümü255.3.3.Miyeloperoksidaz Aktivitesi Tayini255.3.4.Kaspaz-3 aktivite tayini265.3.5.Osteopontin düzeylerinin ölçülmesi265.3.6.N- asetil-β-glukozaminidaz enzim aktivitesi ölçümü265.4.Histolojik İncelemeler265.5.İstatiksel Analiz276.BULGULAR286.1.İdrar Analiz Sonuçları286.2.Böbrek Dokusunda Biyokimyasal Parametrelere Ait Bulgular316.2.1.Miyeloperoksidaz aktivitesi sonuçları326.2.2.Dokuda N-asetil-β-glukozaminidaz enzim aktivitesi sonuçları336.2.3.Kaspaz-3 aktivitesi sonuçları346.2.4.Oksidatif DNA hasarı sonuçları356.2.5.Böbrek dokularında osteopontin düzeyleri366.3.Histolojik Bulgular377.TARTIŞMA VE SONUÇ388.KAYNAKLAR439.EKLER47Ek 1. Etik Kurul Onayı47Ek 2. Kongre Bildirisi4810.ÖZGEÇMİŞ49
2.SUMMARYAim: Urinary system stone disease (USSD) is an important urological disease that can lead to renal dysfunction and permanent renal damage. In this study, we evaluated the preventive and curative effects of Myrtus communis (MC) extract on USSD in rats.Materials and metods: Thirty-two Wistar albino rats of 3 months-old were randomized and divided into 4 groups (n=8); control (C), ethylene glycol (EG), EG+preventive MC, EG+curative MC extract groups. USSD was induced by adding 0.75% EG to drinking water of rats for 8 weeks. At the end of the experiment, 24-hour urine was collected to analyze calcium, citrate, and creatinine levels. In kidney tissues, histological analyses and osteopontin, N-acetyl-β-glucosaminidase (NAG), myeloperoxidase (MPO), caspase-3 activity, oxidative DNA damage (8-OHdG) levels were measured.Results: In 24-hour urine samples, calcium, citrate and creatinine levels were decreased in the EG group, while oxalate levels increased and in the treatment groups these parameters returned to control levels. MPO, 8-OHdG, caspase-3 and NAG activity were significantly increased in tissue and these changes were reversed in both treatment groups. Histological findings also supported biochemical findings.Conclusion: Myrtus communis can prevent crystalluria and kidney damage due to crystal formation and aggregation, when used as either a preventive or therapeutic agent probably through antioxidant properties. Thus, MC might have clinical implications in preventing oxidative renal cell injury and ultimately kidney stone formation.CONTENTSTHESIS APPROVAL iDECLARATION iiACKNOWLEDGMENTS iiiCONTENTS ivLIST OF ABBREVIATIONS AND SYMBOLS viiLIST OF FIGURES viiiTABLE LIST ixPICTURE LIST x1. SUMMARY 12. SUMMARY 23. INTRODUCTION AND PURPOSE 34. Stone Formation Mechanisms 84.1.1. Supersaturation 94.1.2. Nucleation and crystal formation 104.1.3. Crystal aggregation 104.1.4. Crystal retention 114.1.5. Randal plaques 124.2. Stimulating and Suppressing Molecules of Stone Formation 134.3. Ethylene Glycol and Urinary System Stone Model 184.4. Myrtus communis - Mersin Plant 195. MATERIAL AND METHOD 235.1. Preparation of Myrtus communis plant extract 235.2. Working Groups 235.3. Biochemical investigations 255.3.1. Measurement of calcium, citrate, oxalate and creatinine values in urine 255.3.2. Measurement of oxidative DNA damage 255.3.3. Determination of Myeloperoxidase Activity 255.3.4. Determination of caspase-3 activity 265.3.5. Measurement of Osteopontin levels 265.3.6. Measurement of N-acetyl-β-glucosaminidase enzyme activity 265.4. Histological Investigations 265.5. Statistical Analysis 276. RESULTS 286.1. Urine Analysis Results 286.2. Findings of Biochemical Parameters in Kidney Tissue 316.2.1. Results of myeloperoxidase activity 326.2.2. Results of N-acetyl-β-glucosaminidase enzyme activity in tissue 336.2.3. Results of caspase-3 activity 346.2.4. Results of oxidative DNA damage 356.2.5. Osteopontin levels in kidney tissues 366.3. Histological Findings 377. DISCUSSION AND CONCLUSION 388. REFERENCES 439. Appendix 47Annex 1. Ethics Committee Approval 47Annex 2. Congress Declaration 4810 CV 49
2.SUMMARYAim: Urinary system stone disease (USSD) is an important urological disease that can lead to renal dysfunction and permanent renal damage. In this study, we evaluated the preventive and curative effects of Myrtus communis (MC) extract on USSD in rats.Materials and metods: Thirty-two Wistar albino rats of 3 months-old were randomized and divided into 4 groups (n=8); control (C), ethylene glycol (EG), EG+preventive MC, EG+curative MC extract groups. USSD was induced by adding 0.75% EG to drinking water of rats for 8 weeks. At the end of the experiment, 24-hour urine was collected to analyze calcium, citrate, and creatinine levels. In kidney tissues, histological analyses and osteopontin, N-acetyl-β-glucosaminidase (NAG), myeloperoxidase (MPO), caspase-3 activity, oxidative DNA damage (8-OHdG) levels were measured.Results: In 24-hour urine samples, calcium, citrate and creatinine levels were decreased in the EG group, while oxalate levels increased and in the treatment groups these parameters returned to control levels. MPO, 8-OHdG, caspase-3 and NAG activity were significantly increased in tissue and these changes were reversed in both treatment groups. Histological findings also supported biochemical findings.Conclusion: Myrtus communis can prevent crystalluria and kidney damage due to crystal formation and aggregation, when used as either a preventive or therapeutic agent probably through antioxidant properties. Thus, MC might have clinical implications in preventing oxidative renal cell injury and ultimately kidney stone formation.CONTENTSTHESIS APPROVAL iDECLARATION iiACKNOWLEDGMENTS iiiCONTENTS ivLIST OF ABBREVIATIONS AND SYMBOLS viiLIST OF FIGURES viiiTABLE LIST ixPICTURE LIST x1. SUMMARY 12. SUMMARY 23. INTRODUCTION AND PURPOSE 34. Stone Formation Mechanisms 84.1.1. Supersaturation 94.1.2. Nucleation and crystal formation 104.1.3. Crystal aggregation 104.1.4. Crystal retention 114.1.5. Randal plaques 124.2. Stimulating and Suppressing Molecules of Stone Formation 134.3. Ethylene Glycol and Urinary System Stone Model 184.4. Myrtus communis - Mersin Plant 195. MATERIAL AND METHOD 235.1. Preparation of Myrtus communis plant extract 235.2. Working Groups 235.3. Biochemical investigations 255.3.1. Measurement of calcium, citrate, oxalate and creatinine values in urine 255.3.2. Measurement of oxidative DNA damage 255.3.3. Determination of Myeloperoxidase Activity 255.3.4. Determination of caspase-3 activity 265.3.5. Measurement of Osteopontin levels 265.3.6. Measurement of N-acetyl-β-glucosaminidase enzyme activity 265.4. Histological Investigations 265.5. Statistical Analysis 276. RESULTS 286.1. Urine Analysis Results 286.2. Findings of Biochemical Parameters in Kidney Tissue 316.2.1. Results of myeloperoxidase activity 326.2.2. Results of N-acetyl-β-glucosaminidase enzyme activity in tissue 336.2.3. Results of caspase-3 activity 346.2.4. Results of oxidative DNA damage 356.2.5. Osteopontin levels in kidney tissues 366.3. Histological Findings 377. DISCUSSION AND CONCLUSION 388. REFERENCES 439. Appendix 47Annex 1. Ethics Committee Approval 47Annex 2. Congress Declaration 4810 CV 49