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

Öz

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.

Anahtar Kelimeler

• Polidatin
• Apoptozis
• Methotreksat
• Okidadatif stres
• Hepatotoksisite

Etik Beyan

Tüm hayvanları içeren deneysel prosedürler, laboratuvar hayvanlarının bakımı ve kullanımı için kurumsal ve ulusal yönergelere uygun olarak yürütülmüştür.

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

Öz

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.

Anahtar Kelimeler

• Methotrexate hepatotoxicity
• Polydatin
• Oxidative stress
• Apoptosis

Etik Beyan

All experimental procedures involving animals were conducted in accordance with institutional and national guidelines for the care and use of laboratory animals.

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