Leflunomid Methotrexat'a bağlı karaciğer toksisitesini önleyebilir mi?

Year 2018, Volume: 11 Issue: 3, 321 - 327, 28.09.2018

Ufuk Kutluana Nevin Oruç Selma Dinçer Tekekoğlu Neşe Çallı Demirkan Beyza Akdağ Mustafa Yılmaz Nadir Yönetçi Ömer Özütemiz

https://doi.org/10.31362/patd.451731

Abstract

GİRİŞ ve AMAÇ: Uzun dönem Methotrexat kullanımı artmış karaciğer hasarı ve
fibrozis riski ile ilişkilidir. Leflunomid hastalık modifiye edici bir ilaçtır.
Leflunomid nükleer faktör kappa B aktivasyonunun güçlü bir inhibitörüdür. Aynı
zamanda anti-oksidan aktivitesi de vardır. Bu deneysel çalışmada Methotrexat'ın
neden olduğu karaciğer toksisitesinde Leflunomid tedavisinin etkinliği
araştırılmıştır.

YÖNTEM ve GEREÇLER: 39 rat 4 gruba ayrılmıştır. Methotrexat'a bağlı karaciğer
toksisitesi tek doz 20mg/kg Methotrexat'ın periton içine injeksiyonu ile
oluşturulmuştur. Ardından Leflunomid 5 gün boyunca 10 mg/kg dozda verilmiştir.
Ardından serum örnekleri ve homojenize karaciğer örnekleri toplanmıştır. Serum
alanin aminotransferaz, alkalin fosfataz, superoxide dismutaz, myeloperoxidaz
aktivitesi, glutatyon düzeyleri çalışılmış ve histopatolojik değerlendirme
yapılmıştır.

BULGULAR: Leflunomid tedavisi tedavi almayan gruba göre karaciğer
semikantitatif skalaya bağlı histopatolojik değerlendirmede anlamlı düzelme
sağlamıştır (Patolojik skor 1.1+0.7 ve 5.1+2, p<0,01). Leflunomid tedavisi
Kuppfer hücre aktivasyonunu anlamlı derecede iyileştirmiştir. (Aktive Kuppfer
hücre skorunda yükselme 0.2+0.6 ve 2.5+1.01, p = 0.001). Leflunomid tedavisi
alan grupta Methotrexat toksisite grubuna göre serum alanin aminotransferaz,
alkalin fosfataz düzeyleri düşük, glutatyon seviyesi, superoxide dismutaz ve
myeloperoxidaz aktivitesi benzer bulunmuştur.

TARTIŞMA ve SONUÇ: Bu deneysel modelde Leflunomid tedavisi Methotrexat'a bağlı
karaciğer toksisitesini iyileştirmektedir. 

Keywords

Leflunomid, methotrexat, karaciğer toksisitesi

Can Leflunomide prevent Methotrexate induced liver toxicity?

Abstract

INTRODUCTION: Long-term clinical use of Methotrexate is to connect with a
raised risk of liver injury and fibrosis. Leflunomide is a is a
disease-modifying drug. Leflunomide has a powerful inhibitory effect on nuclear
factor kappa B activation. Leflunomide also presents antioxidant activity. In
this experimental study, we aimed to investigate the effects of Leflunomide
treatment on Methotrexate -induced hepatotoxicity.

METHODS: Thirty-nine rats were divided into 4 groups. A single dose of 20mg/kg
Methotrexate was injected intraperitoneally for Methotrexate-induced
hepatotoxicity. After induction, Leflunomide (10 mg/kg) was administered into
the stomach for consecutive 5 days. Then, serum samples and homogenated liver
tissues were collected for analyzed serum alanine aminotransferase, alkaline
phosphatase, superoxide dismutase activity, myeloperoxidase activity,
glutathione levels and assessment of histopathology.

RESULTS: Leflunomide treatment significantly ameliorated total histopathologic
score according to semiquantitative scale compared to the untreated group,
(Pathological score 1.1+0.7 versus 5.1+2 respectively, p<0,01). Leflunomide
treatment significantly ameliorated Kuppfer cell activation. (Elevation of the
activated Kupffer cells score were 0.2+0.6 and 2.5+1.01 respectively, p =
0.001). The serum alanine aminotransferase, alkaline phosphatase levels were
lower and glutathione levels, myeloperoxidase activity, and superoxide
dismutase activity were similar between Leflunomide treated and untreated
Methotrexate toxicity groups.

DISCUSSION AND CONCLUSION: Leflunomide treatment ameliorated Methotrexate
induced liver toxicity in an experimental model.

Keywords

Leflunomide, methotrexate, liver toxicity

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