Ahmet AKTAS, Suleyman KOC, Mustafa OZKARACA, Bilal SAHIN

Melatonin ve Mikofenolat Mofetilin Wistar Sıçanlarında Takrolimus Tarafından İndüklenen Nefrotoksisiteye Karşı Koruyucu Etkisi

Takrolimus güçlü ve iyi tolere edilen bir ilaç olmasına rağmen; bazı yan etkileri vardır. Melatonin ve mikofenolat mofetil (MMF), ilaca bağlı hasara karşı bazı koruyucu özelliklere sahiptir. Biz bu çalışmada sıçanlarda Takrolimus kaynaklı nefrotoksisiteye karşı melatonin ve MMF’nin koruyucu etkisini değerlendirmeyi amaçladık. Hayvanlar beş eşit gruba ayrıldı (n=6): Kontrol grubu (tedavi edilmemiş), grup II Takrolimus, grup III Takrolimus +melatonin, grup IV Takrolimus + MMF ve grup V Takrolimus + melatonin + MMF. Takrolimus, günde bir kez 2 mg/ kg oral olarak uygulandı. Melatonin ve MMF, sırasıyla günde bir kez 10 mg/kg ve 40 mg/kg oral olarak uygulandı. Takrolimus grubunda böbrek dokusu malondialdehit (MDA), toplam oksidatif stress (TOS), interlökin-1 ve tümör nekroz faktör-alfa düzeyleri daha yüksek, katalaz ve toplam antioksidatif stress (TAS) düzeyleri daha düşüktü. Takrolimus grubunda glomerüler konjesyon, intertübüler kanama, hiyalin oluşumu, dejeneratif-nekrotik tübül epiteli ve mononükleer hücre infiltrasyonu gibi ciddi histopatolojik değişiklikler görüldü. Takrolimus ile birlikte melatonin ve MMF kullanılan gruplarda belirgin bir iyileşme oldu. Takrolimusun oksidatif stres yoluyla nefrotoksisiteye neden olduğu gösterilmiştir. Melatonin ve MMF birlikte veya ayrı ayrı böbreği Takrolimusun neden olduğu oksidatif stres hasarına karşı korumaktadır.

Protective Effect of Melatonin and Mycophenolate Mofetil Against Nephrotoxicity Induced by Tacrolimus in Wistar Rats

Although Tacrolimus (TAC) is a potent and well-tolerated drug, it has some side effects. Melatonin and mycophenolate mofetil (MMF) have some protective properties against drug-induced damage. We aimed to evaluate TAC-induced nephrotoxicity and the protective effect of melatonin and MMF against this injury in rats. The animals were divided into five equal groups (n=6): Control group (untreated), group II TAC, group III as the TAC + melatonin, group IV as the TAC + MMF, and group V as the TAC + melatonin + MMF. TAC was applied orally, 2 mg/ kg once daily. Melatonin and MMF were applied orally 10 mg/kg once and 40 mg/kg once daily, respectively. In the TAC group, kidney tissue malondialdehyde (MDA), total oxidative status (TOS), interleukin-1, and tumor necrosis factor-alpha levels were higher, and catalase and total antioxidant status (TAS) levels were lower. Severe histopathologic changes such as glomerular congestion, intertubular hemorrhage, hyaline formation, degenerative-necrotic tubules epithelium, and mononuclear cell infiltration were seen in the TAC group. There was a clear improvement in the groups in which melatonin and MMF were used together with TAC. It was shown that TAC causes nephrotoxicity through oxidative stress. Melatonin and MMF together or separately protect the kidney against oxidative stress damage caused by TAC

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