Protective Effects of Morin Against Paracetamol-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis Pathways

Abstract

Objective: Paracetamol (PCM), although a widely used and non-prescription effective analgesic and antipyretic, can cause nephrotoxicity by causing kidney damage at high doses. Morin (MRN) is a flavonoid found in white mulberry and cranberry, with low toxicity and prominent antioxidant, anti-inflammatory, and antiapoptotic properties. This study aimed to investigate the effects of MRN on PCM-induced kidney toxicity by biochemical, molecular, and histopathological methods. Materials-Methods: Thirty-five Wistar rats were divided into Control, MRN (100 mg/kg), PCM (1000 mg/kg), PCM+MRN50 (50 mg/kg), and PCM+MRN100 (100 mg/kg) groups (n=7); the substances were administered orally for 6 days. The blood and kidney tissues were evaluated with biochemical (urea, creatinine, MDA, GSH, SOD, CAT, GPx), genetic (NF-κB, TNF-α, Caspase-3, Bax, Bcl-2, KIM-1, AQP2) and histopathological methods. Results: While PCM negatively affected kidney function tests, oxidative stress levels, inflammation, and apoptosis markers and caused kidney damage, MRN suppressed these negative effects at both doses, improved kidney function, antioxidant defense, inflammation, and apoptosis parameters, and reduced histopathological damage. Conclusion: The study found that MRN effectively protected kidney tissue from PCM-induced damage by reversing oxidative stress, inflammation, and apoptosis.

Keywords

• Apoptosis
• Inflammation
• Morin
• Nephrotoxicity
• Oxidative stress
• Paracetamol

Morin’in Oksidatif Stres, İnflamasyon ve Apoptozis Yollarının Modülasyonu Yoluyla Parasetamol Kaynaklı Nefrotoksisiteye Karşı Koruyucu Etkileri

Abstract

Amaç: Paracetamol (PCM), yaygın ve reçetesiz kullanılan etkili bir analjezik ve antipiretik olsa da, yüksek dozlarda böbrek hasarına neden olarak nefrotoksisiteye yol açabilir. Morin (MRN), beyaz dut ve kızılcıkta bulunan, düşük toksisiteye sahip, antioksidan, antiinflamatuvar ve antiapoptotik özellikleriyle öne çıkan bir flavonoiddir. Bu çalışmada, PCM’nin neden olduğu böbrek toksisitesi üzerine MRN'nin etkileri biyokimyasal, moleküler ve histopatolojik yöntemlerle araştırılması amaçlanmıştır. Materyal-Metot: Otuz beş Wistar sıçan, Kontrol, MRN (100 mg/kg), PCM (1000mg/kg), PCM+MRN50 (50mg/kg) ve PCM+MRN100 (100mg/kg) gruplarına ayrılmış (n=7); maddeler 6 gün boyunca oral uygulanmıştır. Alınan kan ve böbrek dokuları biyokimyasal (üre, kreatinin, MDA, GSH, SOD, KAT, GPx), genetik (NF-κB, TNF-α, Caspase-3, Bax, Bcl-2, KIM-1, AQP2) ve histopatolojik yöntemlerle değerlendirilmiştir. Bulgular: PCM böbrek fonksiyon testlerini, oksidatif stres düzeylerini, inflamasyon ve apoptoz belirteçlerini olumsuz etkileyip böbrek hasarı oluştururken; MRN her iki dozda bu olumsuz etkileri baskılayarak böbrek fonksiyonu, antioksidan savunma, inflamasyon ve apoptoz parametrelerini iyileştirmiş, histopatolojik hasarı azaltmıştır. Sonuç: Çalışmada MRN'nin oksidatif stresi, inflamasyonu ve apoptozu tersine çevirerek böbrek dokusunu PCM kaynaklı hasardan etkili bir şekilde koruduğu bulunmuştur.

Keywords

• Apoptozis
• İnflamasyon
• Morin
• Nefrotoksisite
• Oksidatif stres
• Parasetamol

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