Therapeutic potential of morin hydrate in methotrexate-induced liver in experimental rats: regulation of organ function and alleviation of oxidative stress

Year 2025, Volume: 50 Issue: 1, 211 - 220, 31.03.2025

Tahir Kahraman , Şeyda Seçgin , Muhammad Nasir Bhaya , Mehmet Fatih Bozkurt , Hikmet Keleş , Sarab Hayder Weli Weli , İdris Türel

https://doi.org/10.17826/cumj.1612553

Abstract

Purpose: Methotrexate (MTX) is an antineoplastic agent with a wide clinical use. However, its complications in tissues cause limitations. The effects of many compounds have been studied in reducing the toxicity of MTX in liver tissue. There are limited studies on the elimination of this damage with morin hydrate (MH) flavonoid. In this study, we investigated the effect of MH in MTX-induced hepatoxicity with a focus on oxidative stress.
Materials and Methods: In the experiment, 32 female rats were grouped as Control, MTX, MH, MTX+MH (n=8). On the first day of the study, MTX 20 mg/kg single dose was administered ip. MH was administered 100 mg/kg by gavage for 10 days. On the 11th day, biochemical and histopathological analyses were performed on liver tissues from rats. All data were presented with statistical comparison.
Results: Serum AST, ALT and LDH levels were highest in the MTX group and lower in the MTX+MH group. MH increased glutathione peroxidase (GPX), reduced glutathione (GSH) and total antioxidant capacity (TAC) levels, but had no regulatory effect on superoxide dismutase (SOD) level. Additionally, MH significantly lowered malondialdehyde (MDA) levels and reduced total oxidant capacity (TOC). Histopathological findings included inflammation, congestion, degeneration, mononuclear cell clusters and dead cells. Tissue damage was most severe in the MTX group, whereas these effects were attenuated in the MTX+MH group.
Conclusion: Our results indicated that MH may be a potential therapeutic agent in MTX-induced acute liver injury.

Keywords

Antioxidant, Hepatoxicity, Liver Function Test, Methotrexate, Morin Hydrate, Oxidative Stress

Ethical Statement

The study was carried out with the decision of the local ethics committee of Bolu Abant Izzet Baysal University Animal experiments dated 01/08/2022 and decision numbered 2020/12/A-1. The rats used in the study were obtained from of Bolu Abant Izzet Baysal University Experimental Animals Application and Research Centre .

Thanks

We would like to thank everyone who contributed to this article.

Deneysel sıçanlarda metotreksat ile indüklenmiş karaciğerde morin hidratın terapötik potansiyeli: organ fonksiyonlarının düzenlenmesi ve oksidatif stresin azaltılması

Abstract

Amaç: Metotreksat (MTX) geniş klinik kullanımı olan antineoplastik bir ajandır. Bununla birlikte, dokulardaki komplikasyonları sınırlamalara neden olmaktadır. MTX'in karaciğer dokusundaki toksisitesini azaltmada birçok bileşikle çalışılmıştır. Morin hidrat (MH) flavonoidi ile bu hasarın giderilmesi konusunda sınırlı sayıda çalışma bulunmaktadır. Bu çalışmada MTX ile indüklenen hepatoksisitede oksidatif strese odaklanılarak MH'nin etkisi araştırıldı.
Gereç ve Yöntem: Deneyde 32 dişi sıçan Kontrol, MTX, MH, MTX+MH olarak gruplandırıldı (n=8). Çalışmanın ilk gününde MTX 20 mg/kg tek doz ip olarak uygulandı. MH 10 gün boyunca 100 mg/kg gavaj yoluyla uygulandı. 11. günde sıçanlardan alınan karaciğer dokuları üzerinde biyokimyasal ve histopatolojik analizler yapıldı. Tüm veriler istatistiksel karşılaştırma ile sunulmuştur.
Bulgular: Serum AST, ALT ve LDH düzeyleri MTX grubunda en yüksek, MTX+MH grubunda ise daha düşüktü. MH glutatyon peroksidaz (GPX), indirgenmiş glutatyon (GSH) ve toplam antioksidan kapasite (TAC) düzeylerini artırırken, süperoksit dismutaz (SOD) düzeyi üzerinde düzenleyici bir etkisi olmamıştır. Ayrıca, MH malondialdehit (MDA) seviyelerini önemli ölçüde düşürmüş ve toplam oksidan kapasiteyi (TOC) azaltmıştır. Histopatolojik bulgular arasında enflamasyon, konjesyon, dejenerasyon, mononükleer hücre kümeleri ve ölü hücreler yer almıştır. Doku hasarı en şiddetli MTX grubunda görülürken, MTX+MH grubunda bu etkiler hafiflemiştir.
Sonuç: Sonuçlarımız MH'nin MTX ile indüklenen akut karaciğer hasarında potansiyel bir terapötik ajan olabileceğini göstermiştir.

Keywords

Antioksidan, Hepatoksisite, Karaciğer Fonksiyon Testi, Metotreksat, Morin Hidrat, Oksidatif Stres

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