Investigation of the Effects of Rutin on Sodium Valproate-Induced Lung Damage in Rats

Abstract

Sodium valproate (SVP) is a drug widely used in epilepsy, migraine, and bipolar disorders. In addition to its therapeutic properties, it has toxic effects on many organs in high doses and prolonged intake. Rutin flavonoid derivative is a natural antioxidant and has been successfully used in many toxications. In the present study, it was aimed to investigate the effects of rutin on SVP-induced lung injury. In the study, 35 Sprague Dawley rats were divided into five equal groups as control, routine, SVP, SVP+Rutin 50 and SVP+Rutin 100 and oral administration was continued for 14 days. At the end of the study, lung tissue was obtained and oxidative stress (MDA, GSH, SOD, CAT, GPx, Nrf-2, HO-1), endoplasmic reticulum stress (ATF-6, PERK), inflammation (NF-ĸB, TNF-α), apoptosis (Bax, Bcl-2, Caspase-3) and autophagy (Beclin-1) parameters were analyzed. The data obtained showed that SVP weakened the defense system by decreasing antioxidant enzyme activities and increased lipid peroxidation, inflammation, apoptosis, and autophagy, leading to increased cell damage. It was determined that SVP and rutin 50 and rutin 100 doses strengthened the antioxidant defense system, suppressed lipid peroxidation, endoplasmic reticulum stress, inflammation, apoptosis, and autophagy, and were effective in protecting the cell from damage. As a result, it was determined that rutin use was beneficial against SVP-induced lung injury.

Keywords

• Lung damage
• Rat
• Rutin
• Sodium valproate

Ratlarda Sodyum Valproat Kaynaklı Akciğer Hasarı Üzerine Rutin’in Etkilerinin Araştırılması

Abstract

Sodium valproat (SVP), başta epilepsi olmak üzere migren ve bipolar bozukluklarda yaygın kullanılan bir ilaçtır. Tedavi edici özelliği yanı sıra yüksek doz ve uzun süre alımlarda çoğu organda toksik etki göstermektedir. Rutin flavanoit türevi doğal bir antioksidandır ve birçok toksikasyonda başarı ile kullanılmıştır. Sunulan çalışmada SVP kaynaklı akciğer hasarı üzerine rutin’ in etkilerinin araştırılması amaçlanmıştır. Çalışmada 35 Sprague Dawley rat kontrol, Rutin, SVP, SVP+Rutin 50 ve SVP+Rutin 100 olmak üzere beş eşit gruba ayrılarak 14 gün oral yolla uygulamalar devam etmiştir. Çalışma sonunda akciğer dokusu alınarak oksidatif stres (MDA, GSH, SOD, CAT, GPx, Nrf-2, HO-1), endoplazmik retikulum stresi (ATF-6, PERK), inflamasyon (NF-ĸB, TNF-α), apoptoz (Bax, Bcl-2, Caspase-3) ve otofaji (Beclin-1) parametreleri incelenmiştir. Elde edilen veriler SVP’ nin antioksidan enzim aktivitelerini azaltarak savunma sistemini zayıflattığını, lipid peroksidasyonu, inflamasyonu, apoptozisi ve otofajiyi artırarak hücrede hasarın artmasına neden olduğu göstermiştir. SVP ile birlikte rutin 50 ve rutin 100 dozlarının antioksidan savunma sistemini güçlendirdiği, lipid peroksidasyonunu, endoplasmik retikulum stresini, inflamasyonu, apoptoz ve otofajiyi baskılayarak hücreyi hasardan korumada etkili olduğu tespit edildi. Sonuç olarak SVP kaynaklı akciğer hasarına karşı rutin kullanımının faydalı olduğu belirlendi.

Keywords

• Akciğer hasarı
• Rat
• Rutin
• Sodyum valproat

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