Osman CAN, Süleyman Sami ÇAKIR, Çiğdem VURAL, Fatma Ceyla ERALDEMİR, Mustafa ÇEKMEN, Alper ÖTÜNÇTEMUR

Asetaminofenin indüklediği nefrotoksisiteye karşı montelukastın önleyici etkisi: Deneysel bir çalışma

Amaç: Bir astım ilacı olan Montelukast, dokular üzerinde anti-inflamatuar etkiye sahiptir. Sıçan modellerinde montelukastın (MK) asetaminofen (APAP) ile indüklenen böbrek hasarı üzerindeki tedavi edici etkisini araştırmayı amaçladık. Gereç ve Yöntemler: Yirmi dört sıçan rastgele her biri altı hayvandan oluşan dört gruba ayrıldı. APAP intraperitoneal olarak 1000 mg/kg/gün tek doz olarak uygulandı. Tedavi grubundaki MK dozu 10 mg/kg olup APAP sonrası oral gavaj ile uygulandı. Diğer gruplar APAP + Salin grubu ve kontrol grubuydu. Nefrotoksisiteyi belirlemek için doku malondialdehit (MDA), indirgenmiş glutatyon (GSH) ve Nitrik oksit (NO) seviyelerini ölçtük. Bulgular: APAP grubundaki serum üre ve kreatinin seviyeleri kontrol ve APAP + MK gruplarındaki sıçanlara göre anlamlı derecede yüksek ölçüldü. APAP ile tedavi edilen sıçanlarda GSH seviyesi önemli ölçüde azaldı. Bununla birlikte, MK verilmesi tedavi grubunda GSH seviyesini önemli ölçüde arttırdı. Tek başına APAP ile tedavi edilen sıçanlardaki doku MDA seviyeleri kontrol grubu ve APAP + MK grubuna kıyasla önemli ölçüde yüksekti. NO seviyesi, APAP ile tedavi edilen grupta yükselmiş olarak ölçüldü. Bununla birlikte, MK tedavi grubundaki NO seviyeleri, APAP ile tedavi edilen gruptan önemli ölçüde düşüktü. Ayrıca, tek başına APAP grubuna kıyasla MK tedavi grubunda bazı morfolojik geri kazanımlar gözlendi. Sonuç: MK’nin APAP kaynaklı renal toksisite ve disfonksiyonu üzerinde faydalı etkileri vardır. Ancak uygun kullanımı ve etkileri göstermek için klinik çalışmalara ihtiyaç vardır.

Anahtar Kelimeler:

Asetaminofen, Böbrek, Montelukast, Nefrotoksisite, Oksidatif stres

Preventive effects of montelukast against acetaminophen-induced nephrotoxicity: An experimental study

Objective: Montelukast, an asthma drug, has an anti-inflammatory effect on tissues. We aimed to investigate therapeutic effect of montelukast (MK) on acetaminophen (APAP) - induced renal damage in rat models. Material and Methods: Twenty-four rats were randomly divided into four groups of six animals each. APAP was administered intraperitoneally as a single dose of 1000 mg/kg/day. In the treatment group, MK dose was 10 mg/kg and administered by oral gavage after APAP. The other groups were APAP + Saline group and the control group. We measured tissue malondialdehyde (MDA), reduced glutathione (GSH), and Nitric oxide (NO) levels to determine the nephrotoxicity. Results: Serum Blood Urea Nitrogen (BUN) and creatinine levels were measured significantly higher in APAP group than rats in the control and APAP + MK groups. The level of GSH was significantly diminished in APAP-treated rats. However, the administration of MK significantly increased the level of GSH in the MK treatment group. Tissue MDA levels in rats treated with APAP alone were significantly higher compared to the control group and APAP + MK group. The level of NO was measured as elevated in APAP treated group. However, NO levels in the MK treatment group were significantly lower than APAP treated group. Furthermore, some morphological recoveries were observed in the MK treatment group compared to APAP alone group. Conclusion: MK has beneficial effects on APAP-induced renal toxicity and dysfunction. However, clinical studies are needed to demonstrate appropriate use and effects.

Keywords:

Acetaminophen, Kidney, Montelukast, Nephrotoxicity, Oxidative stress,

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