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Protective Effects of Polydatin in Methotrexate-Induced Liver Toxicity in Rats; Multi-Pathway Analysis

Sıçanlarda Metotreksat ile İndüklenen Karaciğer Toksisitesinde Polidatinin Koruyucu Etkileri; Çoklu Yolak Analizi

Selman Gencer(Aksaray Eğitim ve Araştırma Hastanesi)0000-0003-3936-4146
Özge Kandemir(AKSARAY ÜNİVERSİTESİ, AKSARAY TEKNİK BİLİMLER MESLEK YÜKSEKOKULU)0000-0001-8884-4168
Nurhan Akaras(AKSARAY ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, HİSTOLOJİ VE EMBRİYOLOJİ ANABİLİM DALI)0000-0002-8457-9448
Hasan Şimşek(AKSARAY ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, FİZYOLOJİ ANABİLİM DALI)
Pages
244–254
Publication Date
2026-07-01
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Findings demonstrate polydatin’s multi-target protection against MTX induced liver injury through mitigating oxidative stress, inflammation, apoptosis, and enhancing regeneration, supporting its adjunctive therapeutic potential.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:This study evaluated polydatin's protective effects against methotrexate (MTX)-induced hepatotoxicity in rats.
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Key Findings & Data:Thirty-five Wistar albino rats were divided into (n=7): Control, Polydatin-only (100 mg/kg), MTX-only (20 mg/kg), MTX + Polydatin (50 mg/kg), and MTX + Polydatin (100 mg/kg).
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Conclusion & Impact:Findings demonstrate polydatin’s multi-target protection against MTX induced liver injury through mitigating oxidative stress, inflammation, apoptosis, and enhancing regeneration, supporting its adjunctive therapeutic potential.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Polidatin · Apoptozis · Methotreksat

Abstract

This study evaluated polydatin's protective effects against methotrexate (MTX)-induced hepatotoxicity in rats. Thirty-five Wistar albino rats were divided into (n=7): Control, Polydatin-only (100 mg/kg), MTX-only (20 mg/kg), MTX + Polydatin (50 mg/kg), and MTX + Polydatin (100 mg/kg). Treatments lasted 7 days. MTX administration significantly increased serum AST/ALT levels, hepatic malondialdehyde (MDA), and pro-inflammatory/apoptotic markers (NF-κB, TNF-α, Bax, Caspase-3 mRNA), while decreasing anti-apoptotic Bcl-2 and tissue-repair signals (Wnt3 mRNA). Co-treatment with polydatin dose-dependently reversed these effects: the 100 mg/kg dose notably normalized AST/ALT and MDA levels more effectively than 50 mg/kg (p<0.05), while both doses comparably suppressed TNF-α, Bax, and Caspase-3. Polydatin (100 mg/kg) significantly elevated Bcl-2 and Wnt3 expression versus lower-dose treatment (p<0.05). Antioxidant defenses (SOD, CAT, GPx, GSH) were also restored in a dose-responsive manner. Histopathology confirmed severe inflammation and cellular damage in MTX groups, whereas polydatin groups showed near-normal liver architecture. Findings demonstrate polydatin’s multi-target protection against MTX induced liver injury through mitigating oxidative stress, inflammation, apoptosis, and enhancing regeneration, supporting its adjunctive therapeutic potential.

Özet

Bu çalışma, polidatinin metotreksat (MTX) ile indüklenen hepatotoksisiteye karşı koruyucu etkilerini sıçanlarda değerlendirmiştir. Toplam 35 Wistar albino sıçan şu gruplara ayrılmıştır: Kontrol, yalnızca polidatin (100 mg/kg), yalnızca MTX (20 mg/kg), MTX + polidatin (50 mg/kg) ve MTX + polidatin (100 mg/kg). Tedaviler 7 gün süreyle uygulanmıştır. MTX uygulaması, serum AST/ALT düzeylerinde, hepatik malondialdehit (MDA) düzeylerinde ve proinflamatuvar/apoptotik belirteçlerde (NF-κB, TNF-α, Bax, Kaspaz-3 mRNA) anlamlı artışa neden olurken; antiapoptotik Bcl-2 ve doku onarımı ile ilişkili sinyaller (Wnt3 mRNA) azalmıştır. Polidatin ile birlikte uygulama bu etkileri doza bağımlı olarak tersine çevirmiştir. 100 mg/kg doz, AST/ALT ve MDA düzeylerini 50 mg/kg doza kıyasla daha etkili şekilde normalize etmiştir (p<0,05), ancak her iki doz da TNF-α, Bax ve Kaspaz-3 düzeylerini benzer şekilde baskılamıştır. Ayrıca, 100 mg/kg polidatin uygulaması, düşük doza kıyasla Bcl-2 ve Wnt3 ekspresyonunu anlamlı olarak artırmıştır (p<0,05). Antioksidan savunma sistemleri (SOD, CAT, GPx, GSH) de doza bağımlı şekilde yeniden düzelmiştir. Histopatolojik inceleme, MTX gruplarında belirgin inflamasyon ve hücresel hasarı doğrularken, polidatin uygulanan gruplarda karaciğer mimarisinin normale yakın düzeyde korunduğunu göstermiştir. Elde edilen bulgular, polidatinin oksidatif stresi azaltma, inflamasyonu ve apoptozu baskılama ve rejenerasyonu artırma yoluyla MTX’e bağlı karaciğer hasarına karşı çok hedefli koruyucu etki gösterdiğini ve bu nedenle adjuvan tedavi açısından potansiyel taşıdığını ortaya koymaktadır.

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Cite This Article

Gencer, S., Kandemir, Ö., Akaras, N., Şimşek, H. (2026). Protective Effects of Polydatin in Methotrexate-Induced Liver Toxicity in Rats; Multi-Pathway Analysis. Türk Doğa ve Fen Dergisi, Cilt: 15 Sayı: 2, 244–254. https://doi.org/10.46810/tdfd.1771398

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