THE AMELIORATING EFFECTS OF BILBERRY ON METHOTREXATE-INDUCED INTESTINAL INJURY

Year 2023, , 455 - 462, 26.12.2023

Gökçen Kerimoğlu , Gamze Bilgin , Servet Kerimoğlu , Nihal Türkmen Alemdar , Selim Demir , Yüksel Aliyazıcıoğlu

https://doi.org/10.24938/kutfd.1347778

Cited By: 1

Abstract

Objective: Methotrexate (MTX) is a folic acid analogue chemotherapeutic used in the treatment of some malignant tumors and autoimmune diseases. In addition to its antitumoral properties, it can also exhibit toxic effects on the kidney and intestines. Bilberry (BB) fruit is a potent natural antioxidant rich in anthocyanidins. The purpose of this study was to investigate the potential ameliorating effects of BB against MTX-induced intestinal damage using biochemical and histological methods.
Material and Methods: Twenty-one adult female Sprague Dawley rats were divided into three equal groups. No procedure was performed on the control group (ControlG), while the MTX group (MTXG) and MTX+BB extract group (MTX+BBG) received a single intraperitoneal dose of 30 mg/kg MTX on the first day of the experiment. MTX+BBG also received 200 mg/kg BB extract by oral gavage once daily for five days starting on the first day of the experiment. Half the intestinal tissues removed from the duodenal region at the experiment were used for biochemical evaluation, and the other half for histological examination.
Results: Malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), and 8-oxo-2′-deoxyguanosine (8- OHdG) values were all higher in MTXG intestinal tissues than in ControlG. MDA, TOS, OSI, and 8-OHdG values were lower in MTX+BBG than in MTXG. In addition, caspase-3 levels in MTXG were higher than those in both ControlG and MTX+BBG, while total antioxidant status (TAS) values were lower. In terms of histology, villous hemorrhage, inflammatory cell infiltration, fusion, and degeneration in the villus epithelium were present in MTXG intestinal tissue, and the total damage score was also high. Improvement in all these parameters was present in MTX+BBG.
Conclusion: Orally administered BB extract can improve MTX-induced intestinal damage through its antioxidant and anti-inflammatory effects.

Keywords

Antioxidant, intestine, methotrexate, oxidative stress, bilberry

Metotreksatın İndüklediği İntestinal Hasar Üzerine Yaban Mersininin İyileştirici Etkileri

Abstract

Amaç: Metotreksat (MTX), bazı malign tümörlerin ve otoimmün hastalıkların tedavisinde kullanılan folik asit analoğu bir kemoterapötiktir. Antitümoral etkilerinin yanında karaciğer, böbrek ve bağırsaklar üzerine toksik etkiler de gösterebilir. Yaban mersini (YM), güçlü ve doğal bir antioksidan olan antosiyaninlerden zengin bir meyvedir. Bu çalışma; MTX ile indüklenen intestinal hasara karşı YM ekstraktının olası iyileştirici etkilerini biyokimyasal ve histolojik olarak araştırmayı amaçlamaktadır.
Gereç ve Yöntemler: Çalışmada kullanılan 21 adet Spraque Dawley ırkı erişkin dişi sıçan, 3 eşit gruba ayrıldı. Kontrol grubu (KontrolG)’na hiçbir işlem uygulanmadı. MTX grubu (MTXG)’na ve MTX+YM ekstraktı grubu (MTX+YMG)’na deneyin ilk günü tek doz 30 mg/kg MTX intraperitoneal olarak uygulandı. MTX+YMG’na, ilave olarak deneyin ilk gününden itibaren 5 gün, günde bir kez oral gavaj ile 200 mg/kg YM ektraktı uygulandı. Deney sonunda duodenal bölgeden alınan intestinal dokuların yarısı biyokimyasal, diğer yarısı histolojik olarak değerlendirildi.
Bulgular: MTXG bağırsak dokularında; malondialdehid (MDA), total oksidan kapasite (TOS), oksidatif stres indeksi (OSI) ve 8-oxo-2′-deoxyguanosine (8-OHdG) değerleri KontrolG’na göre yüksekti. MTX+YMG’nun MDA, TOS, OSI ve 8-OHdG değerleri ise MTXG’na göre azalmıştı. İlave olarak MTXG’nun Kaspaz 3 seviyesi hem ControlG’na hem MTX+YMG’na göre yüksek; total antioksidan durum (TAS) seviyeleri ise düşüktü. Histolojik olarak MTXG bağırsak dokusunun villuslarında hemoraji, inflamatuvar hücre infiltrasyonu, füzyon ve villus epitelinde dejenerasyon vardı ve total hasar skoru da yüksekti. MTX+YMG’nda ise tüm bu patolojilerde hafifleme mevcuttu.
Sonuç: Oral olarak uygulanan YM ekstraktı; antioksidan ve antienflamatuvar etkileri ile MTX’in indüklediği bağırsak hasarını iyileştirebilir.

Keywords

Antioksidan, bağırsak, metotreksat, oksidatif stress, yaban mersini

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