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DENEYSEL DİYABET MODELİNDE NEFROPATİNİN ERKEN DÖNEMİNDE SPESİFİK ANJİOTENSİNII RESEPTÖR ANTAGONİSTİ LOSARTANIN ETKİLERİ

THE EFFECT OF SPECIFIC ANGIOTENSIN RECEPTOR ANTAGONIST LOSARTAN ON DIABETIC NEPHROPATHY IN DIABETIC RAT MODEL

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Abstract (2. Language): 
Angiotensin converting enzyme inhibitors prevent the development of diabetic nephropathy by both blocking the renin-angiotensin system and increasing bradykinin levels through inhibition of the kininase II enzyme. Angiotensin receptor antagonists have specific effect on the renin angiotensin system and do not inhibit kininase II enzyme activity. In this study we aimed to investigate the effect of losartan on diabetic nephropathy and to compare it with captopril therapy. Fifty four female Wistar rats, 10-14 weeks old, enrolled in the study. Rats were made diabetic by intraperitoneal injection of streptosotocin in pH 4.5 sodium citrate buffer and did not receive any antidiabetic treatment. Following the first month of injection rats were separated into three groups: The first group received losartan 10 mg/kg via an orogastric catheter, the second group received captopril 50 mg/l in drinking water, and the third one served as the diabetic control group. Twenty four hour urine samples were collected before and after the first mouth of treatment in separate metabolic cages in order to measure urinary albumin, heparan sulphate, and creatinine excretions. Serum glucose and creatinine levels were determined from the blood samples collected via the intracardiac route. The non-diabetic controlgroup consisted of six healthy and age matched female rats. Urinary albumin excretion rates were similar at the first month, before the beginning of treatment, among the losartan, captopril, and diabetic control groups (952±689 mg/day, 970±547mg/day, 910±514 mg/day, respectively). Following the second month urinary albumin excretion rate significantly increased in the control group (1724±945 mg/day, p<0.005). The urinary albumin excretion rates were comparable between losartan and captopril groups, both being significantly lower than that of the control group (778±221 mg/day and 719±341 mg/day, respectively , p<0.05). Urinary heparan sulphate excretion, creatinine clearance and serum creatinine levels were not different among the three groups. In conclusion, losartan prevented the progressive increase in urinary albumin excretion rate in diabetic rats. The effects of losartan and captopril treatment were found to be similar.
Abstract (Original Language): 
Diyabetik nefropati gelişim sürecinde, anjiotensin dönüştürücü enzim inhibitörlerinin olumlu etkileri hem renin-anjiotensin sisteminin bloke edilmesi, hem de kininaz II enzimi inhibisyonu ile bradikinin düzeylerinin artması yoluyla oluşmaktadır. Kininaz II enzim aktivitesi üzerinde belirgin etkisi olmayan, anjiotensin II tip I reseptör antagonistlerinin diyabetik nefropati sürecindeki etkileri tam anlamıyla ortaya konulamamıştır. Bu çalışmanın amacı, losartanın diyabetik nefropati sürecindeki etkilerini araştırmak ve kaptopril ile karşılaştırmaktır. Çalışmaya 54 adet 10-14 haftalık dişi Wistar rat alındı. Raflarda pH 4.5 sodyum sürat tamponu içinde streptozotosin 65mg/kg periton içine verilerek diyabet oluşturuldu ve antidiyabetik tedavi uygulanmadı. Enjeksiyondan bir ay sonra ratlar üç gruba ayrıldı. Birinci gruba 10mg/kg losartan gavaj ile, ikinci gruba 50 mg/l kaptopril içme suyu içerisinde verildi. Diğer ratlar diyabetik kontrol grubu olarak izlendi .Tedavi başlangıcında ve bir aylık tedavi sonunda ratlar metabolik kafeslere alınarak, 24 saatlik idrar toplandı, bu örneklerde albumin, heparan sülfat ve kreatinin değerleri ölçüldü. İntrakardiyakyolla alınan kan örneklerinde, serum glukoz ve kreatinin düzeyleri çalışıldı. Altı adet sağlıklı ve aynı yaşta rat ile sağlıklı kontrol grubu oluşturuldu. Birinci ay sonunda, tedavi başlamadan önce, losartan, kaptopril ve diyabetik kontrol gruplarında idrarda albumin itrahı benzer oranlardaydı (sırası ile 952±689 mg/gün, 970±547 mg/gün, 910±514 mg/gün). Kontrol grubunda ikinci ay sonunda albumin itrahı belirgin olarak artarken (1724±945mg/gün, p<0.005), losartan ve kaptopril gruplarında hafif bir azalma gözlendi. Bu değerler kendi aralarında farksız, kontrol grubuna göre anlamlı ölçüde düşük olarak bulundu (sırası ile 778±221 mg/gün ve 719±341 mg/gün , p<0.05). İdrarda heparan sülfat itrahı, kreatinin klirensi ve serum kreatinin düzeyleri açısından anlamlı farklılık gözlenmedi. Sonuç olarak diyabetik rotlarda losartan tedavisi ile albümin itrahındaki artış durdurulabilmektedir. Diyabetik ratlarda losartan ve kaptopril tedavisinin etkileri bakılan parametreler açısından birbirleri ile eşdeğer bulunmuştur.
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