Nephroprotective effect of Resveratrol against Methotrexate -induced renal toxicity in female rats

Abstract

The study purposed to appraise the nephroprotective effects of resveratrol-(RES) in relation to methotrexate-(MTX)-induced renal toxicity in female rats. The animals were allocated into three groups with six in each group: control, MTX:(15 mg/kg, only a dose, i.p), MTX+RES group: (15 mg/kg MTX, only a dose, i.p + 20 mg/kg RES, only a dose daily, oral gavage, 7 days). The nephroprotective efficacy was interpreted by measuring biochemical parameters such as serum renal function markers (uric acid, BUN and creatinine), total oxidant (TOS) and antioxidant status (TAS) in renal homogenates. Moreover, the effect of RES on kidneys was appraised by histopathological and immunohistochemical analyzes. In MTX-induced rats, RES treatment exhibited its nephroprotective effects with a significant increase in renal TAS as well as a significant decrease in serum BUN and renal TOS levels. In parallel with the biochemical data, it was observed that RES had a protective effect in the histological staining findings. Immunohistochemically, it was determined that TNF-α, one of the indicators of systemic inflammatory response, decreased with RES-treatment. The findings of the study show that RES administration 1 hour before MTX injection to rats has a curative effect on renal damage.

Keywords

• Methotrexate
• Resveratrol
• Renal toxicity
• female rats

Dişi sıçanlarda Resveratrol'ün Metotreksat ile indüklenen renal toksisiteye karşı nefroprotektif etkisi

Abstract

Reaktif oksijen türlerinin (ROS) güçlü bir temizleyicisi olan resveratrolün (RES), böbrek hastalıkları da dahil olmak üzere çeşitli metabolik bozukluklara karşı koruyucu etkisi olduğu bildirilmektedir. Bu çalışma, dişi sıçanlarda metotreksat (MTX) ile indüklenen renal toksisitede resveratrolün nefroprotektif etkilerini değerlendirmeyi amaçlamaktadır. Çalışma, her grupta altı adet rat olacak şekilde üç gruba ayrıldı: Kontrol, MTX: (15 mg/kg, tek doz, i.p), MTX + RES grubu: (15 mg/kg MTX, tek doz, i.p + 20 mg/ kg RES, günde tek doz, oral gavaj, 7 gün). Serum renal fonksiyon belirteçleri (ürik asit, BUN ve kreatinin), renal homojenatlarda toplam oksidan (TOS) ve antioksidan durumu (TAS) gibi biyokimyasal parametreler ölçülerek nefroprotektif etkinlik yorumlandı. Ayrıca RES'in böbrekler üzerindeki etkisi histopatolojik ve immünohistokimyasal analizlerle değerlendirildi. MTX ile indüklenen ratlarda RES tedavisi, serum BUN, kreatinin ve renal TOS düzeylerinde anlamlı azalmanın yanında renal TAS'ta anlamlı bir artışla nefro-koruyucu etkilerini gösterdi. Histolojik boyama bulgularında da biyokimyasal verilere paralel olarak, RES’in koruyucu etkisinin olduğu gözlendi. İmmünhistokimyasal olarak sistemik inflamatuar yanıtın göstergelerinden biri olan TNF-α'nın RES tedavisi ile azaldığı belirlendi. Araştırmanın bulguları, ratlara MTX enjeksiyonundan 1 saat önce RES uygulamasının böbrek hasarı üzerinde iyileştirici etkisi olduğunu göstermektedir.

Keywords

• Metotreksat
• Resveratrol
• Böbrek toksisitesi
• dişi sıçanlar

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