Effects of rosmarinic acid and quercetin on methotrexate-induced liver and small intestine damage in rats

Year 2024, Volume: 49 Issue: 3, 547 - 560, 30.09.2024

Derya Öztürk Okatan , İlyas Ercan Okatan Abdulkadir Kutlu , Elif Şahin , Neslihan Sağlam , Ahmet Alver , Engin Yenilmez

https://doi.org/10.17826/cumj.1430648

Abstract

Purpose: Rosmarinic acid (RA) is a natural phenolic compound with antioxidant and anti-inflammatory effects. Quercetin (QCT) is a powerful antioxidant that prevents oxidative damage and cell death by clearing oxygen radicals. It also has anti-inflammatory effects. In this study, it was aimed to compare the effects of RA and QCT against liver and small bowel damage that may occur due to methotrexate (MTX) use.
Materials and Methods: The study was conducted on a model of MTX-induced liver and small intestine damage in 40 Spraque Dawley male rats. RA and QCT were administered separately and in combination prophylactically (MTX+QCT group, MTX+RA group, MTX+QCT+RA group respectively). At the end of the study, liver and small intestine tissue were removed. Histopathological evaluations were performed using scoring. Malondialdehyde level, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were examined in the tissues.
Results: In the liver tissue, pathological findings of all prophylaxis groups decreased considerably. When compared to the control group, MDA level increased significantly in the MTX, MTX+RA and MTX+RA+QCT groups The SOD and GPX activities of the MTX group decreased significantly when compared to the control group. It was found that GPX activity increased in the MTX+QCT group and SOD activity increased in the MTX+QCT+RA group when compared to the MTX group. In addition, SOD activity was significantly increased in the MTX+QCT+RA group when compared to the MTX+RA and MTX+QCT groups. In the small intestine tissue, pathological findings decreased significantly in the MTX+QCT group. Pathological findings decreased slightly in MTX+RA, MTX+QCT+RA groups. MDA levels were significantly higher in the MTX and MTX+RA+QCT groups when compared to the control group. The SOD and GPX activities of the MTX group decreased significantly compared to the control group. GPX activity decreased significantly in the MTX+QCT and MTX+RA groups when compared to the control group. SOD activity increased significantly in MTX+RA+QCT group when compared to MTX group, GPX activity increased significantly in MTX+RA+QCT group compared to MTX+QCT group.
Conclusion: RA and QCT may be effective in preventing liver damage caused by MTX. It was concluded that QCT may be more effective than RA in preventing small bowel injury caused by MTX.

Keywords

Rosmarinic acid, quercetin, methotrexate, liver, small intestine tissue

Ethical Statement

Ethical approval was obtained for this study from Karadeniz Technical University Animal Experiments Local Ethics Committee with Protocol no: 2022/17.

Supporting Institution

This study received no financial support

Thanks

We presented this study as an oral presentation at the 1th International Congress of Histology and Embryology (NICHE 2022), 26-28 May 2022, Türkiye.

Rosmarinik asit ve kuersetinin sıçanlarda metotreksat kaynaklı karaciğer ve ince bağırsak hasarı üzerine etkileri

Abstract

Amaç: Rosmarinik asit (RA), antioksidan ve antiinflamatuar etkileri olan doğal bir fenolik bileşiktir. Kuersetin (QCT), oksijen radikallerini temizleyerek oksidatif hasarı ve hücre ölümünü önleyen güçlü bir antioksidandır. Aynı zamanda anti-inflamatuar etkileri de vardır. Bu çalışmada metotreksat (MTX) kullanımına bağlı oluşabilecek karaciğer ve ince bağırsak hasarına karşı RA ve QCT'nin etkilerinin karşılaştırılması amaçlandı.
Gereç ve Yöntem: Çalışma, 40 Spraque Dawley erkek sıçanda MTX'in neden olduğu karaciğer ve ince bağırsak hasarı modeli üzerinde gerçekleştirildi. RA ve QCT profilaktik olarak ayrı ayrı ve kombinasyon halinde uygulandı (sırasıyla MTX+QCT grubu, MTX+RA grubu, MTX+QCT+RA grubu). Çalışmanın sonunda karaciğer ve ince bağırsak dokusu çıkarıldı. Histopatolojik değerlendirmeler skorlama kullanılarak yapıldı. Dokularda malondialdehit düzeyi, süperoksit dismutaz (SOD) ve glutatyon peroksidaz (GPX) aktiviteleri incelendi.
Bulgular: Karaciğer dokusunda tüm profilaksi gruplarının patolojik bulgularında belirgin azalma görüldü. MTX, MTX+RA ve MTX+RA+QCT gruplarında MDA düzeyi kontrol grubuna göre arttı. MTX grubunun SOD ve GPX aktiviteleri kontrol grubuna göre azaldı. MTX grubuna göre MTX+QCT grubunda GPX aktivitesinin, MTX+QCT+RA grubunda ise SOD aktivitesinin arttığı tespit edildi. MTX+QCT+RA grubunda SOD aktivitesi, MTX+RA ve MTX+QCT gruplarına göre arttı. İnce bağırsak dokusunda patolojik bulgular MTX+QCT grubunda azaldı. MTX+RA, MTX+QCT+RA gruplarında patolojik bulgular bir miktar azaldı. MTX ve MTX+RA+QCT gruplarında MDA düzeyleri kontrol grubuna göre yüksekti. MTX grubunun SOD ve GPX aktivitelerinde kontrol grubuna göre azalma görüldü. GPX aktivitesi MTX+QCT ve MTX+RA gruplarında kontrol grubuna göre azaldı. MTX+QCT+RA grubunda MTX grubuna göre SOD aktivitesinin arttığı tespit edildi. GPX aktivitesi MTX+RA+QCT grubunda MTX+QCT grubuna göre arttı.
Sonuç: MTX'in neden olduğu karaciğer hasarını önlemede RA ve QCT'nin etkili olabileceği sonucuna varıldı. MTX'in neden olduğu ince bağırsak hasarını önlemede QCT'nin RA'dan daha etkili olabileceği sonucuna varıldı.

Keywords

Rosmarinik asit, kuersetin, metotreksat, karaciğer, ince bağırsak

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