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

Year 2023, Volume: 30 Issue: 3, 334 - 342, 23.09.2023

Sibel Çiğdem Tuncer , Cihan Gür , Nurhan Akaras , Fatih Mehmet Kandemir

https://doi.org/10.17343/sdutfd.1251167

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

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

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