Yaban Mersini Ekstresinin Metotreksat Kaynaklı Hepatotoksisite Üzerine Etkilerinin Araştırılması

Year 2023, , 519 - 524, 31.12.2023

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

https://doi.org/10.35440/hutfd.1367773

Abstract

Amaç: Metotreksat (Mtx), kanser ve otoimmün hastalıkların tedavisinde yaygın olarak kullanılmaktadır. Ancak Mtx, kendisi gibi birçok kemoterapötiğin metabolizmasından sorumlu olan karaciğerde toksisiteye neden olabilir. Yaban mersini (Ym) meyvesi, yapısında yoğun olarak bulunan fenolik bileşikler sayesinde antioksidan ve antienflamatuvar etkiye sahiptir. Bu çalışma, Ym ekstresinin, Mtx kaynaklı hepatotoksisiteye olan etkilerini araştırmayı amaçlamakta-dır.
Materyal ve metod: Çalışma için 21 adet Spraque Dawley ırkı erişkin sıçan, sayıca eşit üç gruba bölündü. Bir gruba, deneyin ilk günü tek doz 30 mg/kg intraperitoneal (ip.) Mtx verildi (MtxG). Diğer gruba tek doz 30 mg/kg ip. Mtx ve beş gün boyunca günde bir kez oral gavajla 200 mg/kg Ym ekstresi verildi (Mtx+YmG). Kontrol grubuna ise herhangi bir işlem yapılmadı (KG). Deney sonunda alınan karaciğer dokularının bir kısmı histolojik olarak değer-lendirilerek skorlanırken diğer kısmı da biyokimyasal olarak değerlendirildi.
Bulgular: MtxG’nin karaciğer dokularında malondialdehid (MDA) ve kaspaz 3 düzeyleri KG’ye göre yüksekti. KG’ye göre anlamlı olmamakla birlikte MtxG’de, 8-hidroksi-2′-deoksiguanozin (8-OHdG) ve oksidatif stres indeksi (OSİ)’nde artış; süperoksit dismutaz (SOD), katalaz (CAT) ve total antioksidan kapasite (TOS)’de ise azalma mevcut-tu. Mtx+YmG’de MDA düzeyleri MtxG’ye göre azaldı. Bu grupta, kaspaz 3, OSI ve 8-OHdG düzeylerinde de MtxG'ye göre istatistiksel olarak anlamlı olmayan belirgin bir azalma görüldü. Ayrıca bu gruptaki SOD seviyesi KG’ye göre düşükken CAT ve total antioksidan kapasite (TAS) seviyeleri ise MtxG’ye göre istatistiksel anlamlı olmasa da yüksekti. MtxG’de; total hasar skorunda, hepatositlerdeki vakuolizasyon/dejenerasyon/piknoziste, Kupffer hücrelerinde ve vazodilatasyon/konjesyonda kontrole göre artış mevcuttu. Mtx+YmG’de ise tüm bu histopatolojik bulgularda ve total hasar skorunda azalma mevcuttu.
Sonuç: Oral yolla uygulanan Ym ekstresi, sıçan karaciğerindeki Mtx kaynaklı oksidatif stresi, apoptozu ve bunların neden olduğu hepatotoksisiteyi azaltabilir.

Keywords

Karaciğer, metotreksat, oksidatif stress, yaban mersini

Investigation of the Effects of Bilberry Extract on Methotrexate-Induced Hepatotoxicity

Abstract

Background: Methotrexate (Mtx) is widely used in the treatment of cancer and autoimmune diseases. But it can cause toxicity in the liver, which is responsible for the metabolism of many chemotherapeutics such as Mtx. Bilberry (Bb) fruit has antioxidant and anti-inflammatory effects thanks to the phenolic compounds it contains. This study aims to investigate the effects of oral Bb extract on Mtx-induced hepatotoxicity.
Materials and Methods: For the study, 21 Spraque Dawley adult rats were divided into three groups equal in number. One group was given a single dose of 30 mg/kg intraperitoneal (ip.) Mtx on the first day of the experi-ment (MtxG). The other group was given a single dose of 30 mg/kg ip. Mtx and 200 mg/kg Bb extract by oral gavage once a day for five days (Mtx+BbG). No procedure was applied to the control group (CG). While some of the liver tissues taken at the end of the experiment were evaluated and scored histologically, the other part was evaluated biochemically.
Results: Malondialdehyde (MDA) and caspase 3 levels were higher in liver tissues of MtxG than CG. Although it is not significant according to CG, there was an increase in 8-hydroxy-2'-deoxyguanosine (8-OHdG) and oxidative stress index (OSI), but a decrease in superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (TOS) in MtxG. In Mtx+BbG, MDA levels decreased compared to MtxG. In this group, a nonsignificant statististical decrease was also observed in caspase 3, OSI and 8-OHdG levels compared to MtxG. In addition, while the SOD level in this group was lower than in CG; CAT and total antioxidant status (TAS) levels were higher than in MtxG, although not statistically significant. In MtxG, there was an increase in total damage score, vacuoliza-tion/degeneration/pyknosis in hepatocytes, Kupffer cells and sinusoidal vasodilation/congestion compared to the control. In Mtx+BbG, there was a decrease in all these histopathological findings and the total damage score.
Conclusions: Orally administered Bb extract may reduce Mtx-induced oxidative stress, apoptosis, and the hepato-toxicity caused by them in rat liver.

Keywords

Liver, methotrexate, oxidative stress, bilberry

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