Osajin is a promising candidate for sepsis-induced brain damage via suppression of the 8-OHdG/Bax/Caspase-3 pathway in a rat model of sepsis

Year 2025, Volume: 8 Issue: 2, 191 - 196, 21.03.2025

Mohammad Alhilal , Serkan Yıldırım , Hüseyin Serkan Erol , Suzan Alhilal , Metin Kılıçlıoğlu , Berrah Gözegir , Murat Koç , Mesut Bünyami Halıcı

https://doi.org/10.32322/jhsm.1614590

Abstract

Aims: We examined the protective effect of the natural product osajin against sepsis-induced brain damage by targeting the 8-hydroxydeoxyguanosine (8-OHdG)/Bcl-2-associated×protein (Bax)/caspase-3 pathway in the brain tissue of septic rats.
Methods: Osajin was isolated from Maclura pomifera fruit, the structure was confirmed, and a rat model of brain damage was established by the cecal ligation and puncture (CLP) method. Osajin was administered to the animals with sepsis-associated brain damage at 150 and 300 mg/kg. Following euthanasia, histopathological examination, detection of 8-OHdG by immunohistochemistry, and the estimation of Bax and caspase-3 expression using an immunofluorescent technique in the brain tissue were performed.
Results: Histopathological examination revealed the presence of severe inflammation, marked degeneration, and necrosis in the brains of rats with sepsis. The results of immunohistochemical and immunofluorescent assays revealed that the CLP technique induced marked 8-OHdG, Bax, and caspase-3 expression in the brain tissues of septic rats compared with those in healthy rats. Osajin administration at a dose of 150 mg/kg (p<0.05) and 300 mg/kg (p=0.0022) reversed the histopathological changes and significantly ameliorated the increased 8-OHdG, Bax, and caspase-3 expression compared with that in septic rats.
Conclusion: The histopathological, immunohistochemical, and immunofluorescent evidence indicates that osajin can reverse brain damage caused by sepsis by inhibiting the 8-OHdG/Bax/caspase-3 pathway. Accordingly, this natural product represents a promising candidate for the management of brain damage in septic patients.

Keywords

Bax, caspase-3, osajin, sepsis, brain damage, 8-OHdGs

Ethical Statement

Ethical approval was obtained from the Ethics Committee of Animal Experiments at Ataturk University (Code 133, Date 1.09.2015).

Supporting Institution

Ataturk University under the code PRJ2015/298.

Thanks

This study was supported by Ataturk University under the code PRJ2015/298.

Osajin, sıçan sepsis modelinde 8-OHdG/Bax/Kaspaz-3 yolunun bastırılması yoluyla sepsis ile indüklenen beyin hasarı için umut verici bir adaydır

Abstract

Amaçlar: Doğal ürün olan osajinin, sepsis kaynaklı beyin hasarına karşı koruyucu etkisini, sepsisli sıçanların beyin dokusundaki 8-hidroksideoksiguanozin (8-OHdG)/Bcl-2 ile ilişkili × protein (Bax)/kaspaz-3 yolunu hedef alarak inceledik.
Metotlar: Osajin, Maclura pomifera'nın meyvesinden izole edilip yapısı doğrulandı. Çekal ligasyon-punksiyon (CLP) yöntemi ile sıçanlarda beyin hasarı modeli oluşturuldu. Osajin, sepsise bağlı beyin hasarı olan hayvanlara 150 ve 300 mg/kg dozlarda uygulanmıştır. Ötenazi sonrasında histopatolojik inceleme, immünohistokimya ile 8-OHdG'nin tespiti ve immünfloresan teknik kullanılarak Bax ve kaspaz-3 ekspresyonunun tahmini beyin dokusunda yapıldı.
Bulgular: Histopatolojik incelemede sepsisli sıçanların beyinlerinde şiddetli düzeyde inflamasyon, belirgin dejenerasyon ve nekroz görüldü. İmmünohistokimyasal ve immünfloresan analizlerin bulguları, CLP tekniğinin, sağlıklı sıçanlarla karşılaştırıldığında sepsisli sıçanların beyin dokularında belirgin 8-OHdG, Bax ve kaspaz-3 ekspresyonunu indüklediğini ortaya çıkardı. 150 mg/kg (p < 0.05) ve 300 mg/kg (p = 0.0022) dozlarda osajin'in uygulanması, histopatolojik değişiklikleri tersine çevirdiği ve sepsisli sıçanlarla kıyaslandığında artan 8-OHdG, Bax ve kaspaz-3 ekspresyonunu önemli ölçüde iyileştirdiği gözlendi.
Sonuç: Histopatolojik, immünohistokimyasal ve immünfloresan kanıtlar, osajin'in, 8-OHdG/Bax/kaspaz-3 yolunu inhibe ederek sepsisin neden olduğu beyin hasarını tersine çevirebileceğini göstermektedir. Buna göre bu doğal ürünün, sepsisli hastalardaki beyin hasarının tedavisi için umut verici bir aday olabileceği gösterilmiştir.

Keywords

Bax, Kaspaz-3, Osajin, Sepsis, Beyin hasarı, 8-OHdG

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