Can Leflunomide prevent Methotrexate induced liver toxicity?

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

doi:10.31362/patd.451731

TR EN

Leflunomid Methotrexat'a bağlı karaciğer toksisitesini önleyebilir mi?

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

References

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Details

Primary Language

English

Subjects

-

Journal Section

Research Article

Authors

Ufuk Kutluana ^*
Türkiye

Nevin Oruç This is me
Türkiye

Selma Dinçer Tekekoğlu This is me
Türkiye

Neşe Çallı Demirkan
Türkiye

Beyza Akdağ This is me
Türkiye

Mustafa Yılmaz
Türkiye

Nadir Yönetçi This is me
Türkiye

Ömer Özütemiz This is me
Türkiye

Publication Date

September 28, 2018

Submission Date

February 3, 2018

Acceptance Date

August 9, 2018

Published in Issue

Year 2018 Volume: 11 Number: 3

DOI

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

IZ

https://izlik.org/JA45DD26SF

APA

Kutluana, U., Oruç, N., Dinçer Tekekoğlu, S., Çallı Demirkan, N., Akdağ, B., Yılmaz, M., Yönetçi, N., & Özütemiz, Ö. (2018). Can Leflunomide prevent Methotrexate induced liver toxicity? Pamukkale Medical Journal, 11(3), 321-327. https://doi.org/10.31362/patd.451731

AMA

1.Kutluana U, Oruç N, Dinçer Tekekoğlu S, et al. Can Leflunomide prevent Methotrexate induced liver toxicity? Pam Med J. 2018;11(3):321-327. doi:10.31362/patd.451731

Chicago

Kutluana, Ufuk, Nevin Oruç, Selma Dinçer Tekekoğlu, et al. 2018. “Can Leflunomide Prevent Methotrexate Induced Liver Toxicity?”. Pamukkale Medical Journal 11 (3): 321-27. https://doi.org/10.31362/patd.451731.

EndNote

Kutluana U, Oruç N, Dinçer Tekekoğlu S, Çallı Demirkan N, Akdağ B, Yılmaz M, Yönetçi N, Özütemiz Ö (September 1, 2018) Can Leflunomide prevent Methotrexate induced liver toxicity? Pamukkale Medical Journal 11 3 321–327.

IEEE

[1]U. Kutluana et al., “Can Leflunomide prevent Methotrexate induced liver toxicity?”, Pam Med J, vol. 11, no. 3, pp. 321–327, Sept. 2018, doi: 10.31362/patd.451731.

ISNAD

Kutluana, Ufuk - Oruç, Nevin - Dinçer Tekekoğlu, Selma - Çallı Demirkan, Neşe - Akdağ, Beyza - Yılmaz, Mustafa - Yönetçi, Nadir - Özütemiz, Ömer. “Can Leflunomide Prevent Methotrexate Induced Liver Toxicity?”. Pamukkale Medical Journal 11/3 (September 1, 2018): 321-327. https://doi.org/10.31362/patd.451731.

JAMA

1.Kutluana U, Oruç N, Dinçer Tekekoğlu S, Çallı Demirkan N, Akdağ B, Yılmaz M, Yönetçi N, Özütemiz Ö. Can Leflunomide prevent Methotrexate induced liver toxicity? Pam Med J. 2018;11:321–327.

MLA

Kutluana, Ufuk, et al. “Can Leflunomide Prevent Methotrexate Induced Liver Toxicity?”. Pamukkale Medical Journal, vol. 11, no. 3, Sept. 2018, pp. 321-7, doi:10.31362/patd.451731.

Vancouver

1.Ufuk Kutluana, Nevin Oruç, Selma Dinçer Tekekoğlu, Neşe Çallı Demirkan, Beyza Akdağ, Mustafa Yılmaz, Nadir Yönetçi, Ömer Özütemiz. Can Leflunomide prevent Methotrexate induced liver toxicity? Pam Med J. 2018 Sep. 1;11(3):321-7. doi:10.31362/patd.451731

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Jurnal Farmasi SYIFA

https://doi.org/10.63004/jfs.v1i2.200

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