Ali Tuğrul AKIN, Emin KAYMAK, Emel ÖZTÜRK, Tayfun CEYLAN, Betül YALÇIN, Kemal Erdem BAŞARAN, Derya KARABULUT, Züleyha DOĞANYİĞİT, Saim ÖZDAMAR, Birkan YAKAN

Hipoksiye bağlı bağırsak hasarına karşı klorokin tedavisinin hafifletici etkileri: histolojik ve immünohistokimyasal bir çalışma

Amaç: Hipoksi, TNF-α (Tumor necrosis factor- alpha), IL-6 ve IFN-y gibi inflamatuvar sitokinler ve apoptotik düzenleyici proteinler tarafından indüklenen apoptoz neticesinde bağırsağın mukozal bütünlüğünün bozulmasında önemli bir role sahiptir. Klorokin (CLQ), yeni koronavirüs hastalığında (COVID-19) kullanılan bir ilaçtır ve sıtma ve romatoid artrit gibi birçok inflamatuvar hastalığın tedavisi için yaygın olarak kullanılmaktadır. Bu çalışmada, sıçanların bağırsak mukozasında hipoksi ile indüklenen inflamasyon ve apoptoza bağlı yıkıcı etkilerin CLQ uygulamaları ile azaltılması amaçlanmıştır. Yöntem: Bu amaçla toplam 24 adet Wistar Albino rat rastgele üç gruba ayrılmıştır; Grup I: Kontrol grubu (n=8), Grup II: Hipoksi (n=8) ve Grup III: Hipoksi + CLQ (n=8). Kontrol grubu normal atmosferik ortamda (%21 O2), hipoksi ve hipoksi+CLQ grupları oksijen seviyelerinin 28 gün boyunca %10 seviyelerinde tutulabilmesi için pleksiglas kafeslerde barındırılmış ve hipoksi+CLQ grubuna 28 gün boyunca her gün 50 mg/kg dozda CLQ uygulanmıştır. Deney sonunda anestezi altında bağırsak dokuları çıkarılan deney hayvanlarının yaşamlarına son verilmiştir. Bulgular: Histopatolojik değerlendirmeler sonucunda CLQ uygulamalarının, hipoksinin bağırsakta indüklediği histopatolojik etkiler üzerinde iyileştirici özellikler gösterdiği belirlenmiştir. Hipoksi grubunda TNF-α ekspresyonunda artış gözlenirken, hipoksi+CLQ grubunda istatistiksel olarak anlamlı bir azalma tespit edilmiştir. Ayrıca hipoksi+CLQ grubunda Bax ekspresyonunun Hipoksi grubu ile karşılaştırıldığında istatistiksel olarak anlamlı derecede düşük olduğu belirlenmiştir. Bunların aksine, Bcl-2 ekspresyonunun hipoksi+CLQ grubunda hipoksi grubuna göre istatistiksel olarak anlamlı derecede artmış olduğu gözlenmiştir. Sonuç: Hipoksinin barsak mukozasında önemli bir hasara neden olduğunu ve hücreleri apoptoza sürükleyen ciddi bir inflamasyonu tetiklediğini gözlemledik. Klorokinin bağırsak mukozası üzerindeki iyileştirici etkileri göz önüne alındığında, bu anti- enflamatuar ilacın, bağırsakta hipoksinin zararlı etkilerini hafifletmek için klinik olarak kullanım potansiyeline sahip olduğunu düşünmekteyiz.

Mitigative effects of chloroquine treatment against hypoxia-induced intestinal injury: a histological and immunohistochemical study

Objective: Hypoxia has an important role in the disruption of intestinal mucosal integrity because of inflammation and apoptosis induced by inflammatory cytokines such as TNF-α (Tumor necrosis factor-alpha), IL-6 and IFN-y, and apoptotic regulatory proteins. Chloroquine (CLQ) is a drug used in the novel coronavirus disease (COVID-19) and is widely used for the treatment of many inflammatory diseases such as malaria and rheumatoid arthritis. In this study, we aimed to reduce the destructive effects of hypoxia-induced inflammation and apoptosis in the intestinal mucosa of rats with CLQ applications. Methods: For this purpose, a total of 24 Wistar Albino rats were randomly divided into three groups; Group I: Control group (n=8), Group II: Hypoxia (n=8) and Group III: Hypoxia + CLQ (n=8). The control group was housed in plexiglass cages to keep the oxygen levels at 10% levels for 28 days, while the hypoxia and hypoxia+CLQ groups were housed in a normal atmospheric environment (21% O2), and the hypoxia+CLQ group was administered CLQ at a dose of 50 mg/kg every day for 28 days. At the end of the experiment, the intestinal tissues of the experimental animals, were extracted under the anesthesia and they were sacrificed. Results: As a result of histopathological evaluations, it was determined that CLQ applications showed healing properties on the histopathological effects induced by hypoxia in the intestine. While an increase in TNF-α expression was observed in the hypoxia group, a statistically significant decrease was detected in the hypoxia+CLQ group. In addition, Bax expression was found to be statistically significantly lower in the hypoxia+CLQ group when compared to the hypoxia group. On the contrary, it was observed that Bcl-2 expression was statistically significantly increased in the hypoxia+CLQ group compared to the Hypoxia group. Conclusion: We observed that hypoxia causes significant damage to the intestinal mucosa and triggers a severe inflammation that drives cells to apoptosis. Considering the curative effects of chloroquine on the intestinal mucosa, we suggest that this anti-inflammatory drug has a potential to use clinically to alleviate the deleterious effects of hypoxia in the intestine.

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