PROTECTIVE EFFECT OF RUTIN ON OXIDATIVE STRESS, INFLAMMATION AND APOPTOSIS IN VALPROAT-INDUCED GASTRIC TOXICITY

Abstract

Objective Sodium valproate is one of the most commonly used antiepileptic drugs and is toxic after long-term exposure. Long-term exposure to sodium valproate causes an increase in oxidative stress and inflammation in tissues. Rutin is a flavonoid naturally found in many plants with antioxidant, anti-inflammatory, and antiapoptotic effects. This study aimed to investigate the use and possible outcomes of rutin, a natural antioxidant, on gastric tissue damage caused by sodium valproate. Material and Method 35 Wistar albino rats were divided into 5 groups: control, rutin, sodium valproate, sodium valproate+rutin-50mg, and sodium valproate+rutin-100mg. For 14 days, a 500 mg/kg dose of sodium valproate and 50 or 100 mg/kg of rutin were administered by oral gavage. On the 15th day, rats were decapitated and gastric tissues were removed. SOD, CAT, GPx activities, MDA, GSH levels, and oxidative stress damage were analyzed by spectrophotometric method. Inflammation damage by NF-κB, TNF-α, COX-2, and MMP-9 transcription levels and apoptotic damage by Bax, Bcl-2, and Caspase-3 mRNA transcription levels were analyzed by RT-PCR method. Histologic analysis with hematoxylin-eosin staining was also performed to score for congestion, hemorrhage, mucosal damage, cell infiltration and gland dilatation. Results In gastric tissues, MDA level and NF-κB, TNF-α, COX- 2, MMP-9, Bax and Caspase-3 mRNA transcription levels increased (p<0.05), CAT, SOD, GPX activities, GSH level and Bcl-2 mRNA transcription level decreased (p<0.05) in sodium valproate group compared to control group. Rutin administration resulted in a reversal of all these changes due to sodium valproate (p<0.05). Conclusion It was concluded that rutin has potential protective properties against the toxic effect of sodium valproate exposure in gastric tissues.

Keywords

• Valproate
• Oxidative stress
• Inflammation
• Apoptosis
• Gastric Toxicity
• Rutin

SIÇANLARDA SODYUM VALPROAT KAYNAKLI MİDE HASARI ÜZERİNE RUTİN’İN OKSİDATİF STRES, İNFLAMASYON VE APOPTOZ ÜZERİNDEKİ KORUYUCU ETKİLERİNİN ARAŞTIRILMASI

Abstract

Amaç Sodyum valproat, antiepileptik ilaçlardan en yaygın kullanılanlardan birisi olup uzun süreli maruziyet sonucunda toksik etkilidir. Uzun süreli sodyum valproat maruziyeti dokularda özellikle oksidatif stres ve inflamasyon artışına neden olmaktadır. Rutin, birçok bitkide doğal olarak bulunan antioksidan, antiinflamatuvar ve antiapoptotik etkilere sahip bir flavanoiddir. Bu çalışmada, sodyum valproat kaynaklı mide doku hasarı üzerine doğal bir antioksidan olan rutinin kullanımı ve muhtemel etkilerinin araştırılması amaçlanmıştır. Gereç ve Yöntem 35 adet Wistar albino cinsi sıçan kontrol, rutin, sodyum valproat, sodyum valproat+rutin-50mg ve sodyum valproat+rutin-100mg grupları olmak üzere 5 gruba ayrıldı. 14 gün boyunca 500 mg/kg dozda sodyum valproat uygulamasıyla birlikte 50 veya 100 mg/ kg rutin uygulaması oral gavaj yolla yapıldı. 15. günde sıçanlar dekapite edilerek mide dokuları alındı. SOD, KAT, GPx aktiviteleri ile MDA, GSH seviyeleri ile oksidatif stres hasarı spektrofotormetrik yöntem ile analiz edildi. NF-κB, TNF-α, COX-2 ve MMP-9 transkripsiyon düzeyleri ile inflamasyon hasarı ve Bax, Bcl-2, Kaspaz-3 mRNA transkripsiyon düzeyleri ile apoptotik hasar analizi RT-PCR yöntemi ile analiz edildi. Ayrıca konjesyon, hemoraji, mukoza hasarı, hücre infiltrasyonu ve bez dilatasyonu açısından skorlama için hematoksilen-eozin boyama ile histolojik analizler yapıldı. Bulgular Mide dokularında kontrol grubuna göre sodyum valproat grubunda MDA düzeyi ile NF-κB, TNF-α, MMP-9, COX-2, Bax ve Kaspaz-3 mRNA transkripsiyon düzeyleri artmış (p<0.05), KAT, SOD, GPX aktiviteleri ile GSH düzeyi ve Bcl-2 mRNA transkripsiyon düzeyi azalmıştır (p<0.05). Rutin uygulamasıyla birlikte sodyum valproata bağlı tüm bu değişikliklerde tersi yönde aktivite meydana gelmiştir (p<0.05). Sonuç Mide dokularında sodyum valproat maruziyetinin neden olduğu toksik etkiye karşı rutinin potansiyel koruyucu özelliklere sahip olduğu sonucuna varıldı.

Keywords

• Apoptoz
• İnflamasyon
• Mide Toksisitesi
• Oksidatif stres
• Rutin
• Valproat

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